diff --git a/appveyor.yml b/appveyor.yml index 117ddeb..82a1641 100644 --- a/appveyor.yml +++ b/appveyor.yml @@ -1,5 +1,5 @@ environment: - app_version: '7.2.0' + app_version: '7.3.0' version: '%app_version%.{build}' diff --git a/lib/DCI b/lib/DCI index 3129184..3320e0e 160000 --- a/lib/DCI +++ b/lib/DCI @@ -1 +1 @@ -Subproject commit 3129184a261a800df074a5fa0a272a6307ff6de1 +Subproject commit 3320e0e4297f4a7c0c7581399dcc7731f6893293 diff --git a/lib/DCIMatlab/DCIMatlabR2013b6_0.dll b/lib/DCIMatlab/DCIMatlabR2013b6_0.dll deleted file mode 100644 index 22964ce..0000000 Binary files a/lib/DCIMatlab/DCIMatlabR2013b6_0.dll and /dev/null differ diff --git a/lib/DCIMatlab/DCIMatlabR2013b6_1.dll b/lib/DCIMatlab/DCIMatlabR2013b6_1.dll new file mode 100644 index 0000000..e980e22 Binary files /dev/null and b/lib/DCIMatlab/DCIMatlabR2013b6_1.dll differ diff --git a/lib/DCIMatlab/ml_freadtab.dll b/lib/DCIMatlab/ml_freadtab.dll new file mode 100644 index 0000000..8610288 Binary files /dev/null and b/lib/DCIMatlab/ml_freadtab.dll differ diff --git a/lib/DCIMatlab/ml_fwritetab.dll b/lib/DCIMatlab/ml_fwritetab.dll new file mode 100644 index 0000000..fcb04b5 Binary files /dev/null and b/lib/DCIMatlab/ml_fwritetab.dll differ diff --git a/lib/Dimensions b/lib/Dimensions index 443802d..d159e10 160000 --- a/lib/Dimensions +++ b/lib/Dimensions @@ -1 +1 @@ -Subproject commit 443802d74373119a0da12ac271cf4ee51d625d4d +Subproject commit d159e10d47a3ab73242618bc8fe0d85f1e38f8a0 diff --git a/lib/Schema b/lib/Schema index 7eaddcc..ba10b25 160000 --- a/lib/Schema +++ b/lib/Schema @@ -1 +1 @@ -Subproject commit 7eaddcc9b3addfde4c18cbdf392ae8972a43a7d8 +Subproject commit ba10b251d111d6370d04904da2b261acdc7279dd diff --git a/packages.config b/packages.config index 9657859..9a2cf00 100644 --- a/packages.config +++ b/packages.config @@ -1,7 +1,7 @@ - - - - + + + + diff --git a/rakefile b/rakefile index 95ac6a3..5211be0 100644 --- a/rakefile +++ b/rakefile @@ -90,7 +90,7 @@ end def copy_to_lib_dir(target_lib_dir) copy_depdencies lib_dir, target_lib_dir do - copy_dci_dll + copy_files File.join('DCI','x86'), 'dll' copy_schema_xsd copy_dcimatlab_dll copy_dimensions_xml diff --git a/scripts b/scripts index 97d4fc3..1533da9 160000 --- a/scripts +++ b/scripts @@ -1 +1 @@ -Subproject commit 97d4fc353d3e75b97ea765790c1ce0c06f9a9913 +Subproject commit 1533da91c69e9d4fe53c49479f57f11bf458a438 diff --git a/src/matlab_toolbox_core b/src/matlab_toolbox_core index 8a18f57..b69660c 160000 --- a/src/matlab_toolbox_core +++ b/src/matlab_toolbox_core @@ -1 +1 @@ -Subproject commit 8a18f57abeef17a1cc14aa638aeb8512d2a2ebcb +Subproject commit b69660ce8f2169d09ddc397b6ba6723f2e2f4e9b diff --git a/tests/checkHelptextForDirectory.m b/tests/checkHelptextForDirectory.m index 34a57dc..17de0af 100644 --- a/tests/checkHelptextForDirectory.m +++ b/tests/checkHelptextForDirectory.m @@ -4,8 +4,7 @@ function checkHelptextForDirectory(functionDir) % CHECKHELPTEXTFORDIRECTORY(functionDir) % functionDir name of the directory -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 16-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org files=dir([functionDir filesep '*.m']); diff --git a/tests/loop_BasisToolBox.m b/tests/loop_BasisToolBox.m index da4535e..c8b8244 100644 --- a/tests/loop_BasisToolBox.m +++ b/tests/loop_BasisToolBox.m @@ -3,8 +3,7 @@ % % LOOP_BASISTOOLBOX -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 16-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org % prepare logDir if ~exist('log','dir') diff --git a/tests/mergeErrorFlag.m b/tests/mergeErrorFlag.m index 0c50641..730eb57 100644 --- a/tests/mergeErrorFlag.m +++ b/tests/mergeErrorFlag.m @@ -7,9 +7,7 @@ % ErrorFlag double: Maximum of ErrorFlag_tmp % ErrorMessage (string): concatination of all -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 16-Sep-2010 - +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org if isempty(ErrorFlag_tmp) ErrorFlag=0; diff --git a/tests/models/ModelTemplate.pksim5 b/tests/models/ModelTemplate.pksim5 new file mode 100644 index 0000000..082fe71 Binary files /dev/null and b/tests/models/ModelTemplate.pksim5 differ diff --git a/tests/models/asian woman.xml b/tests/models/asian woman.xml index 712641f..b1e40d9 100644 --- a/tests/models/asian woman.xml +++ b/tests/models/asian woman.xml @@ -1,25337 +1,25688 @@ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + - + - + - - K_uptake-K_rec>=0 ? K_uptake-K_rec : 0 + + V_pls_art+V_pls_bon+V_pls_brn+V_pls_cae+V_pls_colasc+V_pls_coldesc+V_pls_colsigm+V_pls_coltrans+V_pls_duo+V_pls_fat+V_pls_tes+V_pls_hrt+V_pls_kid+V_pls_lin+V_pls_lil+V_pls_lje+V_pls_lng+V_pls_mus+V_pls_pan+V_pls_prc+V_pls_prp+V_pls_pve+V_pls_rect+V_pls_skn+V_pls_sin+V_pls_spl+V_pls_sto+V_pls_uil+V_pls_uje+V_pls_ven - - + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + - V_pls_art+V_pls_bon+V_pls_brn+V_pls_cae+V_pls_colasc+V_pls_coldesc+V_pls_colsigm+V_pls_coltrans+V_pls_duo+V_pls_fat+V_pls_tes+V_pls_hrt+V_pls_kid+V_pls_lin+V_pls_lil+V_pls_lje+V_pls_lng+V_pls_mus+V_pls_pan+V_pls_prc+V_pls_prp+V_pls_pve+V_pls_rect+V_pls_skn+V_pls_sin+V_pls_spl+V_pls_sto+V_pls_uil+V_pls_uje+V_pls_ven + K_uptake-K_rec>=0 ? K_uptake-K_rec : 0 + + + + + + + P_1 + P_2 + P_3 + P_4 + P_5 + P_6 + P_7 + P_8 + P_9 + P_10 + P_11 + P_12 + P_13 + P_14 + P_15 + P_16 + + + + + + + + + + + + + + + + + + + + + Weight_blood + Weight_tissue + + + + + + + P_1 + P_2 + P_3 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - M_art + M_sto + M_sin + M_lin + M_pan + M_spl + M_liv + M_lng + M_mus + M_fat + M_skn + M_kid + M_brn + M_hrt + M_bon + M_tes + M_pve + M_ven - - - - - - - - - - - - - - - - - - - - - - + + + + + + Age* 365.25/7 + GA - - + + - + Height>0 ? BW / (Height)^2 : 0 - - + + + + + + 1.6667 * W^0.5 * (H*10)^ 0.5 + + + - + 0.41 - + 51.24 - + 15.4896 - + fQ_art*C_bc_art+fQ_bon*C_bc_bon+fQ_fat*C_bc_fat+fQ_mus*C_bc_mus+fQ_skn*C_bc_skn - - - - - - - - - - + + + + + + + + + + - + fQ_art*C_pls_art+fQ_bon*C_pls_bon+fQ_fat*C_pls_fat+fQ_mus*C_pls_mus+fQ_skn*C_pls_skn - - - - - - - - - - + + + + + + + + + + - + (fQ_art*C_pls_art+fQ_bon*C_pls_bon+fQ_fat*C_pls_fat+fQ_mus*C_pls_mus+fQ_skn*C_pls_skn)*fu - - - - - - - - - - - + + + + + + + + + + + - + (1-HCT)*(fQ_art*C_pls_art+fQ_bon*C_pls_bon+fQ_fat*C_pls_fat+fQ_mus*C_pls_mus+fQ_skn*C_pls_skn) + HCT*(fQ_art*C_bc_art+fQ_bon*C_bc_bon+fQ_fat*C_bc_fat+fQ_mus*C_bc_mus+fQ_skn*C_bc_skn) - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + Volume * Density - - + + - - 0.644569411280264 + + 0.644549336391982 - + Volume - + - + (1-HCT)*V - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + C_pls*fu - - + + - + Volume - + - + HCT*V - - + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + (1 - HCT) * C_pls+HCT * C_bc - - - + + + - + Volume * Density - - + + - - 0.280235711460203 + + 0.280224776435026 - + Volume - + - + (1-HCT)*V - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + C_pls*fu - - + + - + Volume - + - + HCT*V - - + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + (1 - HCT) * C_pls+HCT * C_bc - - - + + + - + 6*EHC_HalfTime - + - + V>0 ? M/V : 0 - - + + - - M/TotalDrugMass + + TotalDrugMass>0 ? M/TotalDrugMass : 0 - - + + - + Volume * Density - - + + - + Qspec * Weight - - + + - - 0.00000000000728*(BW/0.02)^0.75 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - - 0.00000068*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - + SA_pls_int*d_endo - - + + - + 1 - f_int - f_vas - - + + - + 0.032332 - - 7.97746557544493 + + 7.97749307176179 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - 0.00000000000032*BW/0.02 + + SA_pls_int*d_endo - + + - - 1.55E-14*(BW/0.02)^0.75 + + f_lymph*Q*(1-HCT) - + + + - - SA_pls_int*d_endo + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 1.35730748813606 + + 1.35728860419695 - + 0.52156 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - + SA_pls_int*d_endo - - + + - - 0.00000000261*(BW/0.02)^0.75 + + f_lymph*Q*(1-HCT) - + + + - - 0.000000079*BW/0.02 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 15.5617936282565 + + 15.5612579479274 - + 0.79 - + 0.8 - + 0.002 - + + 0.15 + + 0.16 - + 0.18 - - 0.15 + + 0.853 - + 0.92 - - 0.853 + + 0.0016 - + 0.002024 - - 0.0016 - - + 0.135 - + 0.00899999999999998 - + 0.03 - + 0.025901 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - 0.00000000375*(BW/0.02)^0.75 + + SA_pls_int*d_endo - + + - - 0.000000075*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - - SA_pls_int*d_endo + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 0.0114993044792707 + + 0.0114997710656791 - + 0.0896799999999998 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - SA_pls_int*d_endo + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - + + + + + + - - 0.000000198*(BW/0.02)^0.75 + + f_lymph*Q*(1-HCT) - + + + - - 0.00000081*BW/0.02 + + SA_pls_int*d_endo - + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 0.287486332675593 + + 0.287482394891315 - + 0.898334000000001 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - + SA_pls_int*d_endo - - + + - - 0.0000000649*(BW/0.02)^0.75 + + f_lymph*Q*(1-HCT) - + + + - - 0.00000021*BW/0.02 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + 1 - f_int - f_vas - - + + - - (PMA^Hill/(TM50^Hill+PMA^Hill)*(1-GFR_premat)+GFR_premat) * GFR_mat / V_kid_std + + Age <= Age_onset ? 1 : 1 - Decrease_Factor*(Age-Age_onset)^Hill/(TA50^Hill+(Age-Age_onset)^Hill) + + + + + + + + + + GFRspec * Weight_Kidney + + + + + + + (PMA^Hill/(TM50^Hill+PMA^Hill)*(1-GFR_premat)+GFR_premat) * GFR_mat / V_kid_std * Renal_aging_scaling_factor - - - - - - + + + + + + + - + Qspec * Weight - - + + - - 0.353307303441634 + + 0.353343737185662 - - 15 + + 0 - + 44.4 - + + 30 + + + 59 + + 0.11704 - + + 1.5 + + + 15 + + 2.778487 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + V>0 ? M/V : 0 - - + + - + V>0 ? M/V : 0 - - + + - - M/TotalDrugMass + + TotalDrugMass>0 ? M/TotalDrugMass : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + 1.00000000260982 - - Volume + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - + - - Area*d + + Liquid/V - - + + - - 1/GET + + PI*(r1+r2)*L - + + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + 1/GET - - - + - - SteadyStateFillLevel*V/StomachInflowTime + + V*SteadyStateFillLevel - - - - + + - - pH_fasted + + OralApplicationsEnabled ? -LT_sto + Inflow*FillLevelFlag : 0 - + + + + - - V*SteadyStateFillLevel + + w*Liquid*FillLevelFlagNext - - + + + - - OralApplicationsEnabled ? -LT_sto + Inflow*FillLevelFlag : 0 + + SteadyStateFillLevel*V/StomachInflowTime - - - - + + + + - - PI*(r1+r2)*L + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - + + + - - Liquid/V + + Area*d - - + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + Volume - + - - w*Liquid*FillLevelFlagNext + + pH_fasted - - - + - + 0.5 - - 0.5 + + 0.999999963215789 - + + 2 + + 15.0000000391473 - + 1.00000002079922 - - 2 - - - 0.999999963215789 + + 0.5 - + V>0 ? M/V : 0 - - + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + F1*F2*F3 - - - - - - - - - - - - + + + - - F1*(1-F2)*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - (1-F1)*F2*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + (1-F1)*F2*F3 - - - + + + - - F1*F2*(1-F3) + + F1*(1-F2)*F3 - - - + + + - - F1*(1-F2)*F3 + + F1*F2*(1-F3) - - - + + + - - (1-F1)*F2*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - - F1*F2*F3 + + (1-F1)*F2*(1-F3) - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + F1*(1-F2)*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + + + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + LuminalVelocity/SITT_fact - - - + + - - r2_p0 + Height*r2_p1 + + L_p0 + Height*L_p1 - - - + + + - - Ageom*AeffFactor*AeffVariabilityFactor + + V*SteadyStateFillLevel - - - + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + OralApplicationsEnabled ? LT_sto - LT_duo + Inflow*FillLevelFlag - Outflow*Liquid : 0 - + + + + + + + - - Liquid/V + + w*Liquid*FillLevelFlagNext - - + + + - - PI*(r1+r2)*L + + r1_p0 + Height*r1_p1 - - - + + + - - LuminalVelocity/SITT_fact + + 0.02894*V - - + - - L_p0 + Height*L_p1 + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - + + + + - - V*SteadyStateFillLevel + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - + + + - - OralApplicationsEnabled ? LT_sto - LT_duo + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - - - - - + - - w*Liquid*FillLevelFlagNext + + V_Intestine * 0.087 - - - + - - r1_p0 + Height*r1_p1 + + Volume - - - + - - 0.02894*V + + PI*(r1+r2)*L - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + Liquid/V - - - - + + - - Volume + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - + + + + + + + - - V_Intestine * 0.087 + + r2_p0 + Height*r2_p1 - + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + Ageom*AeffFactor*AeffVariabilityFactor - - - - - - - + + + - + 292.6883 - + V>0 ? M/V : 0 - - + + - - (1-F1)*F2*F3 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - F1*(1-F2)*F3 + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - F1*F2*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - (1-F1)*F2*(1-F3) + + F1*F2*F3 - - - + + + - - F1*(1-F2)*(1-F3) + + (1-F1)*F2*F3 - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + F1*(1-F2)*F3 - - - + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + F1*F2*(1-F3) - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + (1-F1)*(1-F2)*F3 - - - - - - - - - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*F2*(1-F3) - - - - + + + - - F1*F2*F3 + + F1*(1-F2)*(1-F3) - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - + + + + + + + + + + + + + + + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - Ageom*AeffFactor*AeffVariabilityFactor + + LuminalVelocity/SITT_fact - - - + + - - w*Liquid*FillLevelFlagNext + + V_Intestine * 0.249 - - - + - + V*SteadyStateFillLevel - - + + - + OralApplicationsEnabled ? LT_duo - LT_uje + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - - - - - + + + + + + + - - L_p0 + Height*L_p1 + + w*Liquid*FillLevelFlagNext - - - + + + - - LuminalVelocity/SITT_fact + + r1_p0 + Height*r1_p1 - - + + + - - PI*(r1+r2)*L + + 0.0031572*V - - - + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - + + + + - - r2_p0 + Height*r2_p1 + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + Volume - - - - - - - + - - Liquid/V + + PI*(r1+r2)*L - - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + L_p0 + Height*L_p1 - - - - + + + - - r1_p0 + Height*r1_p1 + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - Volume + + r2_p0 + Height*r2_p1 - + + + - - V_Intestine * 0.249 + + Ageom*AeffFactor*AeffVariabilityFactor - + + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - 0.0031572*V + + Liquid/V - + + - + 447.9877 - + V>0 ? M/V : 0 - - + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*F3 - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*F2*(1-F3) - - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + F1*(1-F2)*F3 - - - - + + + - + (1-F1)*F2*F3 - - - - - - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - - + + + - + F1*F2*F3 - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - - - - - - - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - F1*(1-F2)*(1-F3) + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - (1-F1)*F2*(1-F3) + + F1*(1-F2)*(1-F3) - - - + + + - - (1-F1)*(1-F2)*F3 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - F1*F2*(1-F3) + + (1-F1)*F2*(1-F3) - - - + + + - - F1*(1-F2)*F3 + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + + + + +
+ + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - PI*(r1+r2)*L + + r1_p0 + Height*r1_p1 - - - + + + - - Liquid/V + + 0.0025102*V - - + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - + + + + - - Ageom*AeffFactor*AeffVariabilityFactor + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - + + + - - L_p0 + Height*L_p1 + + V_Intestine * 0.184 - - - + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + L_p0 + Height*L_p1 - - - - - - - + + + - - V*SteadyStateFillLevel + + Volume - - + - - OralApplicationsEnabled ? LT_uje - LT_lje + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + w*Liquid*FillLevelFlagNext - - - - - - - + + + - - r2_p0 + Height*r2_p1 + + V*SteadyStateFillLevel - - - + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + OralApplicationsEnabled ? LT_uje - LT_lje + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - + + + + + + + - - Volume + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - + + + + + + + - - LuminalVelocity/SITT_fact + + r2_p0 + Height*r2_p1 - - + + + - - V_Intestine * 0.184 + + Ageom*AeffFactor*AeffVariabilityFactor - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - - + - - 0.0025102*V + + Liquid/V - + + - - r1_p0 + Height*r1_p1 + + PI*(r1+r2)*L - - - + + + - - w*Liquid*FillLevelFlagNext + + LuminalVelocity/SITT_fact - - - + + - + 372.9358 - + V>0 ? M/V : 0 - - + + - - F1*F2*(1-F3) + + F1*(1-F2)*(1-F3) - - - + + + - - (1-F1)*F2*(1-F3) + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - F1*(1-F2)*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + F1*F2*F3 - - - - - - - - - - - - - - - - F1*(1-F2)*F3 + + + + + + + (1-F1)*F2*F3 - - - + + + - - (1-F1)*(1-F2)*F3 + + F1*(1-F2)*F3 - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + F1*F2*(1-F3) - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + (1-F1)*F2*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - F1*F2*F3 + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + - - (1-F1)*F2*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - LuminalVelocity/SITT_fact + + r2_p0 + Height*r2_p1 - - + + + - - L_p0 + Height*L_p1 + + r1_p0 + Height*r1_p1 - - - + + + - - V*SteadyStateFillLevel + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - + + + + + + + - - OralApplicationsEnabled ? LT_lje - LT_uil + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + Ageom*AeffFactor*AeffVariabilityFactor - - - - - - - + + + - - w*Liquid*FillLevelFlagNext + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - r1_p0 + Height*r1_p1 + + Liquid/V - - - + + - - 0.0029585*V + + PI*(r1+r2)*L - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + LuminalVelocity/SITT_fact - - - - + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + L_p0 + Height*L_p1 - - - + + + - - V_Intestine * 0.324 + + V*SteadyStateFillLevel - + + - - Volume + + OralApplicationsEnabled ? LT_lje - LT_uil + Inflow*FillLevelFlag - Outflow*Liquid : 0 - + + + + + + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + 0.0029585*V - + - - PI*(r1+r2)*L + + w*Liquid*FillLevelFlagNext - - - + + + - - Ageom*AeffFactor*AeffVariabilityFactor + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - + + + + - - r2_p0 + Height*r2_p1 + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + V_Intestine * 0.324 - - - - - - - + - - Liquid/V + + Volume - - + - + 260.7527 - + V>0 ? M/V : 0 - - + + - - F1*F2*(1-F3) + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + + + + +
+ + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + (1-F1)*(1-F2)*(1-F3) - - - - - - - - - - - - + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + F1*(1-F2)*(1-F3) - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + (1-F1)*F2*(1-F3) - - - + + + - - F1*(1-F2)*(1-F3) + + (1-F1)*(1-F2)*F3 - - - + + + - - (1-F1)*(1-F2)*F3 + + F1*F2*(1-F3) - - - + + + - + F1*(1-F2)*F3 - - - + + + - + (1-F1)*F2*F3 - - - + + + - + F1*F2*F3 - - - + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - - + + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - - - - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - - - + + + + - - (1-F1)*F2*(1-F3) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - V_Intestine * 0.156 + + PI*(r1*r1+r1*r2+r2*r2)/3*L - + + + - - Volume + + V_Intestine * 0.156 - + - - Ageom*AeffFactor*AeffVariabilityFactor + + Volume - - - + - - V*SteadyStateFillLevel + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - + + + + - - OralApplicationsEnabled ? LT_uil - LT_lil + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - - - - - + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + Ageom*AeffFactor*AeffVariabilityFactor - - - - + + + - - 0.0017657*V + + Liquid/V - + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + PI*(r1+r2)*L - - - - - - - + + + - - w*Liquid*FillLevelFlagNext + + LuminalVelocity/SITT_fact - - - + + - - r2_p0 + Height*r2_p1 + + L_p0 + Height*L_p1 - - - + + + - - L_p0 + Height*L_p1 + + V*SteadyStateFillLevel - - - + + - - LuminalVelocity/SITT_fact + + OralApplicationsEnabled ? LT_uil - LT_lil + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - + + + + + + + - - PI*(r1+r2)*L + + w*Liquid*FillLevelFlagNext - - - + + + - - Liquid/V + + r1_p0 + Height*r1_p1 - - + + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + 0.0017657*V - + - - r1_p0 + Height*r1_p1 + + r2_p0 + Height*r2_p1 - - - + + + - + 146.565 - + V>0 ? M/V : 0 - - + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + +
+ + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - + + + + + + + + + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + F1*F2*F3 - - - + + + - + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - - - - - (1-F1)*(1-F2)*(1-F3) - - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + F1*(1-F2)*(1-F3) - - - - - - - - - - - - + + + - - F1*(1-F2)*(1-F3) + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + Volume - - - + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + V_Intestine * 0.08470588 - - - - - - - + - - r2_p0 + Height*r2_p1 + + LuminalVelocity/LITT_fact - - - + + - - Ageom*AeffFactor*AeffVariabilityFactor + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + r2_p0 + Height*r2_p1 - + + + - - Liquid/V + + Ageom*AeffFactor*AeffVariabilityFactor - - + + + - - PI*(r1+r2)*L + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - LuminalVelocity/LITT_fact + + PI*(r1+r2)*L - - + + + - + L_p0 + Height*L_p1 - - - + + + - + V*SteadyStateFillLevel - - + + - + OralApplicationsEnabled ? LT_lil - LT_cae + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - - - - - + + + + + + + - + w*Liquid*FillLevelFlagNext - - - + + + - + r1_p0 + Height*r1_p1 - - - + + + - + 0*V - + - + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - - + + + + - - Volume + + Liquid/V - + + - - V_Intestine * 0.08470588 + + PI*(r1*r1+r1*r2+r2*r2)/3*L - + + + - + 1.8 - + V>0 ? M/V : 0 - - + + - - F1*F2*F3 + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + + F1*F2*F3 + + + + + + + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - - - - - F1*(1-F2)*(1-F3) - - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - - - - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor - - - - + + + - + +
+ + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - - - - - - - - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + + + + + + + + F1*(1-F2)*(1-F3) - - - - + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + Volume - - - - + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + V_Intestine * 0.15529412 - - - + - - V_Intestine * 0.15529412 + + V*SteadyStateFillLevel - + + - - Volume + + OralApplicationsEnabled ? LT_cae - LT_colasc + Inflow*FillLevelFlag - Outflow*Liquid : 0 - + + + + + + + - - r1_p0 + Height*r1_p1 + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - w*Liquid*FillLevelFlagNext + + r2_p0 + Height*r2_p1 - - - + + + - - 0.00098426*V + + Ageom*AeffFactor*AeffVariabilityFactor - + + + - - r2_p0 + Height*r2_p1 + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - V*SteadyStateFillLevel + + Liquid/V - - + + - - OralApplicationsEnabled ? LT_cae - LT_colasc + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + PI*(r1+r2)*L - - - - - - - + + + - + L_p0 + Height*L_p1 - - - + + + - - LuminalVelocity/LITT_fact + + w*Liquid*FillLevelFlagNext - - + + + - - PI*(r1+r2)*L + + r1_p0 + Height*r1_p1 - - - + + + - - Liquid/V + + 0.00098426*V - - + - - Ageom*AeffFactor*AeffVariabilityFactor + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - + + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - - - - - + + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + LuminalVelocity/LITT_fact - + + - + 2.5 - + V>0 ? M/V : 0 - - + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + (1-F1)*F2*(1-F3) - - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + F1*(1-F2)*(1-F3) - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + F1*F2*(1-F3) - - - - + + + - - F1*F2*F3 + + F1*(1-F2)*F3 - - - + + + - - (1-F1)*F2*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - - F1*(1-F2)*F3 + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - F1*F2*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - F1*(1-F2)*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + F1*F2*F3 - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - - - - - - - - - - (1-F1)*F2*(1-F3) + + (1-F1)*F2*F3 - - - + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - V*SteadyStateFillLevel + + r1_p0 + Height*r1_p1 - - + + + - - OralApplicationsEnabled ? LT_colasc - LT_coltrans + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + r2_p0 + Height*r2_p1 - - - - - - - + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + Ageom*AeffFactor*AeffVariabilityFactor - - - - - - - + + + - - r2_p0 + Height*r2_p1 + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + Liquid/V - + + - + PI*(r1+r2)*L - - - + + + - - Volume + + LuminalVelocity/LITT_fact - + + - - V_Intestine * 0.32 + + L_p0 + Height*L_p1 - + + + - - LuminalVelocity/LITT_fact + + w*Liquid*FillLevelFlagNext - - + + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + 0.00020285*V - - - + - - L_p0 + Height*L_p1 + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - + + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - - + + + - - 0.00020285*V + + V_Intestine * 0.32 - + - - r1_p0 + Height*r1_p1 + + Volume - - - + - - w*Liquid*FillLevelFlagNext + + V*SteadyStateFillLevel - - - + + - - Ageom*AeffFactor*AeffVariabilityFactor + + OralApplicationsEnabled ? LT_colasc - LT_coltrans + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - + + + + + + + - - Liquid/V + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - + + + + + + + - + 2.5 - + V>0 ? M/V : 0 - - + + - - (1-F1)*F2*(1-F3) + + (1-F1)*(1-F2)*F3 - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + (1-F1)*F2*(1-F3) - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*(1-F2)*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - F1*F2*F3 + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + - + (1-F1)*F2*F3 - - - + + + - - F1*(1-F2)*F3 + + F1*F2*(1-F3) - - - + + + - - (1-F1)*(1-F2)*F3 + + F1*(1-F2)*F3 - - - + + + - - F1*(1-F2)*(1-F3) + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - - - - - - - - - - - - - F1*F2*(1-F3) + + + + + + + + F1*F2*F3 - - - + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - + Ageom*AeffFactor*AeffVariabilityFactor - - - + + + - - r2_p0 + Height*r2_p1 + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - - - - - + + + + - - PI*(r1+r2)*L + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + Liquid/V - + + - - 0.00023004*V + + PI*(r1+r2)*L - + + + - - V_Intestine * 0.24 + + LuminalVelocity/LITT_fact - + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + L_p0 + Height*L_p1 - - - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + V*SteadyStateFillLevel - - - - + + - - r1_p0 + Height*r1_p1 + + OralApplicationsEnabled ? LT_coltrans - LT_coldesc + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - + + + + + + + - + w*Liquid*FillLevelFlagNext - - - + + + - - V*SteadyStateFillLevel + + 0.00023004*V - - + - - OralApplicationsEnabled ? LT_coltrans - LT_coldesc + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - - - - - + + + - - L_p0 + Height*L_p1 + + V_Intestine * 0.24 - - - + - - LuminalVelocity/LITT_fact + + Volume - - + - - Liquid/V + + r2_p0 + Height*r2_p1 - - + + + - - Volume + + r1_p0 + Height*r1_p1 - + + + - + 2.5 - + V>0 ? M/V : 0 - - + + - - (1-F1)*(1-F2)*F3 + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + - - (1-F1)*F2*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - F1*(1-F2)*(1-F3) + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + F1*F2*F3 - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + (1-F1)*F2*F3 - - - - - - - - - - - - - - - + + + + + + F1*(1-F2)*F3 - - - + + + - - (1-F1)*F2*F3 + + F1*F2*(1-F3) - - - + + + - - F1*F2*(1-F3) + + (1-F1)*(1-F2)*F3 - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + (1-F1)*F2*(1-F3) - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*(1-F2)*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - F1*F2*F3 + +
+ + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - Volume + + PI*(r1*r1+r1*r2+r2*r2)/3*L - + + + - - V_Intestine * 0.135 + + PI*(r1+r2)*L - + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + LuminalVelocity/LITT_fact - - - - - - - + + - - r2_p0 + Height*r2_p1 + + L_p0 + Height*L_p1 - - - + + + - + V*SteadyStateFillLevel - - + + - + OralApplicationsEnabled ? LT_coldesc - LT_colsigm + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - - - - - + + + + + + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + w*Liquid*FillLevelFlagNext - - - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + r1_p0 + Height*r1_p1 - - - - + + + - + 0.00013099*V - + - - w*Liquid*FillLevelFlagNext + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - + + + + - - L_p0 + Height*L_p1 + + Ageom*AeffFactor*AeffVariabilityFactor - - - + + + - - LuminalVelocity/LITT_fact + + V_Intestine * 0.135 - - + - - PI*(r1+r2)*L + + Volume - - - + - + Liquid/V - - + + - + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - + - - Ageom*AeffFactor*AeffVariabilityFactor + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - r1_p0 + Height*r1_p1 + + r2_p0 + Height*r2_p1 - - - + + + - + 2.5 - + V>0 ? M/V : 0 - - + + - + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + F1*F2*F3 - - - + + + - + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - - - - - F1*(1-F2)*(1-F3) - - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + + + + + + + + + + + + + + + F1*(1-F2)*(1-F3) - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - - - - - - - - - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - - - - - PI*(r1*r1+r1*r2+r2*r2)/3*L - - - - + + - + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - - - - - + + + + + + + - + r2_p0 + Height*r2_p1 - - - + + + - + Ageom*AeffFactor*AeffVariabilityFactor - - - + + + - + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - + - + Liquid/V - - + + - - PI*(r1+r2)*L + + L_p0 + Height*L_p1 - - - + + + - - LuminalVelocity/LITT_fact + + PI*(r1+r2)*L - - + + + - - L_p0 + Height*L_p1 + + V_Intestine * 0.055 - - - + - + V*SteadyStateFillLevel - - + + - + OralApplicationsEnabled ? LT_colsigm - LT_rect + Inflow*FillLevelFlag : 0 - - - - - + + + + + - + w*Liquid - - + + - + r1_p0 + Height*r1_p1 - - - + + + - + 0.00071247*V - + - + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - - + + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + - + Volume - + - - V_Intestine * 0.055 + + LuminalVelocity/LITT_fact - + + - + 3.56 - + V>0 ? M/V : 0 - - + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - + + + + + + + + + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - - - - - - - - - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + F1*(1-F2)*(1-F3) - - - - + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - F1*(1-F2)*(1-F3) + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - + + + + - - (1-F1)*F2*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + F1*F2*F3 - - - + + + - - F1*F2*(1-F3) + + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - - (1-F1)*F2*F3 + + F1*F2*(1-F3) - - - + + + - - F1*F2*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + (1-F1)*F2*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - + OralApplicationsEnabled ? LT_rec : 0 - - + + - + V>0 ? M/V : 0 - - + + - - M/TotalDrugMass + + V>0 ? M/V : 0 - - + + - + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + TotalOralDrugMass > 0 ? (M_sto + M_duo + M_uje + M_lje + M_uil + M_lil + M_cae + M_colasc + M_coltrans + M_coldesc + M_colsigm + M_rect + M_fec + Mabs_Mucosa) / TotalOralDrugMass : 0 - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - + Volume * Density - - + + - - 0.000000066*BW/0.02 + + SA_pls_int*d_endo - + + - - SA_pls_int*d_endo + + f_lymph*Q*(1-HCT) - - + + + - - 0.00000000543*(BW/0.02)^0.75 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 0.142902725569453 + + 0.142916401240294 - + 0.361079999999999 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - + P1*SITT+P2 - - - + + + - - SA_pls_int*d_endo + + J_iso_incl_Mucosa-J_iso_duo-J_iso_uje-J_iso_lje-J_iso_uil-J_iso_lil - - + + + + + + - - 0.00000012*BW/0.02 + + SA_pls_int*d_endo - + + - - Q_lymph_incl_Mucosa-Q_lymph_duo-Q_lymph_uje-Q_lymph_lje-Q_lymph_uil-Q_lymph_lil + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - - - - - + + + + + + - - 0.00000000421*(BW/0.02)^0.75 + + Q_lymph_incl_Mucosa-Q_lymph_duo-Q_lymph_uje-Q_lymph_lje-Q_lymph_uil-Q_lymph_lil - + + + + + + - - J_iso_incl_Mucosa-J_iso_duo-J_iso_uje-J_iso_lje-J_iso_uil-J_iso_lil + + f_lymph*Q*(1-HCT) - - - - - - + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - + V_duo+V_uje+V_lje+V_uil+V_lil - - - - - + + + + + - + 126.000000328837 - - 0.607648371912122 + + 0.607678528632753 - + 0.934501 - + Volume - + - + f_vas*(1-HCT)*(V-V_Mucosa) - - - - + + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*(V-V_Mucosa) - - - - + + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*(V-V_Mucosa) - - - + + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume-V_Mucosa - - + + - + f_cell*(V-V_Mucosa) - - - + + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - Q_lymph_intestine * V_seg / V_intestine + + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - Q_lymph_intestine * V_seg / V_intestine + + J_iso_intestine * V_seg / V_intestine - - - + + + - + SA_pls_int*d_endo - - + + - - J_iso_intestine * V_seg / V_intestine + + Q_lymph_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - Q_lymph_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + J_iso_intestine * V_seg / V_intestine - - + + + - + Q_lymph_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - - Q_lymph_intestine * V_seg / V_intestine + + J_iso_intestine * V_seg / V_intestine - - - + + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (M_int + M_cell + M_int_duo + M_cell_duo + M_int_uje + M_cell_uje + M_int_lje + M_cell_lje + M_int_uil + M_cell_uil + M_int_lil + M_cell_lil)/(V_int + V_cell + V_int_duo + V_cell_duo + V_int_uje + V_cell_uje + V_int_lje + V_cell_lje + V_int_uil + V_cell_uil + V_int_lil + V_cell_lil) - - - - - - - - - - - - - - - - - - - - - - - - - - - - P1*LITT+P2 + + + + + + + + + + + + + + + + + + + + + + + + + + + + Volume * Density - - - + + - + V_cae+V_ca+V_ct+V_cd+V_cs+V_rec - - - - - - + + + + + + - - Volume * Density + + P1*LITT+P2 - - + + + - - J_iso_incl_Mucosa-J_iso_cae-J_iso_colasc-J_iso_coltrans-J_iso_coldesc-J_iso_colsigm-J_iso_rect + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - - - - - - + + + + + + - - 0.000000000705*(BW/0.02)^0.75 + + SA_pls_int*d_endo - + + - + Q_lymph_incl_Mucosa-Q_lymph_cae-Q_lymph_colasc-Q_lymph_coltrans-Q_lymph_coldesc-Q_lymph_colsigm-Q_lymph_rect - - - - - - - + + + + + + + - - 0.00000034*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - - SA_pls_int*d_endo + + J_iso_incl_Mucosa-J_iso_cae-J_iso_colasc-J_iso_coltrans-J_iso_coldesc-J_iso_colsigm-J_iso_rect - - + + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - + 2652 - - 0.364624243673881 + + 0.364553665093464 - + 0.708 - + Volume - + - + f_vas*(1-HCT)*(V-V_Mucosa) - - - - + + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*(V-V_Mucosa) - - - - + + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*(V-V_Mucosa) - - - + + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume-V_Mucosa - - + + - + f_cell*(V-V_Mucosa) - - - + + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - Q_lymph_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - - Q_lymph_intestine * V_seg / V_intestine + + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - Q_lymph_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - Q_lymph_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + J_iso_intestine * V_seg / V_intestine - - + + + - - J_iso_intestine * V_seg / V_intestine + + Q_lymph_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - - Q_lymph_intestine * V_seg / V_intestine + + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - + Q_lymph_intestine * V_seg / V_intestine - - - + + + - - SA_pls_int*d_endo + + J_iso_intestine * V_seg / V_intestine - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (M_int + M_cell + M_int_cae + M_cell_cae + M_int_colasc + M_cell_colasc + M_int_coltrans + M_cell_coltrans + M_int_coldesc + M_cell_coldesc + M_int_colsigm + M_cell_colsigm + M_int_rect + M_cell_rect)/(V_int + V_cell + V_int_cae + V_cell_cae + V_int_colasc + V_cell_colasc + V_int_coltrans + V_cell_coltrans + V_int_coldesc + V_cell_coldesc + V_int_colsigm + V_cell_colsigm + V_int_rect + V_cell_rect) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + Volume * Density - - + + - - SA_pls_int*d_endo + + f_lymph*Q*(1-HCT) - - + + + - - 0.0000091*BW/0.02 + + SA_pls_int*d_endo - + + - - 0.00000169*(BW/0.02)^0.75 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 1.67800684756425 + + 1.67762813625727 - + 0.20119 - - Volume * Density + + Liver_Parameter - - + - + Liver_Parameter - + - + Liver_Parameter - + - - Liver_Parameter + + Volume * Density - + + - + V_liv * (IsLiverZonated ? f_periportal : 1) - - - + + + - + Liver_Parameter - + - - J_iso * (IsLiverZonated? f_periportal : 1) + + Liver_Parameter - - - + - - Liver_Parameter + + SA_pls_int*d_endo - + + - - SA_pls_int*d_endo + + Q_lymph * (IsLiverZonated? f_periportal : 1) - - + + + - + Liver_Parameter - + - - Q_lymph * (IsLiverZonated? f_periportal : 1) + + J_iso * (IsLiverZonated? f_periportal : 1) - - - + + + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + pH_cell_Liver - + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Volume * Density - - + + - + V_liv * (IsLiverZonated ? 1 - f_periportal : 0) - - - + + + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - - SA_pls_int*d_endo + + Q_lymph * (IsLiverZonated? 1-f_periportal : 0) - - + + + - + J_iso * (IsLiverZonated? 1-f_periportal : 0) - - - + + + - - Q_lymph * (IsLiverZonated? 1-f_periportal : 0) + + SA_pls_int*d_endo - - - + + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + pH_cell_Liver - + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + f_vas*(1-HCT)*V_org - - - + + + - + (C_pls_prp * V_pls_prp + C_pls_prc * V_pls_prc)/(V_pls_prp+V_pls_prc) - - - - + + + + - + f_vas*HCT*V - - - + + + - + (C_bc_prp * V_bc_prp + C_bc_prc * V_bc_prc)/(V_bc_prp+V_bc_prc) - - - - + + + + - + f_int*V - - + + - + pH_int - + - + (C_int_prp * V_int_prp + C_int_prc * V_int_prc)/(V_int_prp+V_int_prc) - - - - + + + + - + f_cell*V - - + + - + (C_cell_prp * V_cell_prp + C_cell_prc * V_cell_prc)/(V_cell_prp+V_cell_prc) - - - - + + + + - + (C_int_prp * K_water_int_prp * V_int_prp + C_int_prc * K_water_int_prc * V_int_prc)/(V_int_prp+V_int_prc) - - - - - - + + + + + + - + (C_cell_prp * K_water_cell_prp * V_cell_prp + C_cell_prc * K_water_cell_prc * V_cell_prc)/(V_cell_prp+V_cell_prc) - - - - - - + + + + + + - + (C_int_prp * V_int_prp + C_int_prc * V_int_prc + C_cell_prp * V_cell_prp + C_cell_prc * V_cell_prc)/(V_int_prp+V_int_prc+V_cell_prp) - - - - - - - - + + + + + + + + - + Volume * Density - - + + - - 0.000000000301*(BW/0.02)^0.75 + + f_lymph*Q*(1-HCT) - + + + - - 0.000005*BW/0.02 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + SA_pls_int*d_endo - - + + - + 1 - f_int - f_vas - - + + - + Q_sto + Q_sin + Q_lin + Q_pan + Q_spl + Q_liv + Q_mus + Q_fat + Q_skn + Q_kid + Q_brn + Q_hrt + Q_bon + Q_tes - - - - - - - - - - - - - - - - - - 0.827250027390281 - - + + + + + + + + + + + + + + + + + + 0.827079917716317 + + 0.53 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - SA_pls_int*d_endo + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - + + + + + + - - 0.000000111*(BW/0.02)^0.75 + + SA_pls_int*d_endo - + + - - 0.00000055*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 17.7581430145229 - - - 0.013 + + 17.759368464494 - + 0.0238 - + + 0.013 + + 0.0072 - + 0.177 - + 0.811 - + 0.76 - + 0.16 - - 0.022 - - + 0.0049 - + + 0.022 + + 0.0042 - + 0.0078 - + 0.079 - + 0.19 - + 0.666 - + 0.76 - + 0.032804 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - 0.0000000872*(BW/0.02)^0.75 + + SA_pls_int*d_endo - + + - - SA_pls_int*d_endo + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - + + + + + + - - 0.00000065*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 0.148353957961437 + + 0.148304701431509 - + 0.348099999999999 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - + Q_Lymph_sto + Q_Lymph_sin_incl_Mucosa + Q_Lymph_lin_incl_Mucosa + Q_Lymph_pan + Q_Lymph_spl - - - - - + + + + + - + Q_sto + Q_sin + Q_lin + Q_pan + Q_spl - - - - - + + + + + - - 0.693623120538448 + + 0.693640095090257 - + Volume - + - + (1-HCT)*V - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + C_pls*fu - - + + - + Volume - + - + HCT*V - - + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + (1 - HCT) * C_pls+HCT * C_bc - - - + + + - + Volume * Density - - + + - - 0.000000342*(BW/0.02)^0.75 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + SA_pls_int*d_endo - - + + - - 0.00000051*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 2.38281390495198 + + 2.38279235578768 - + 0.10856 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - 0.0000000000961*(BW/0.02)^0.75 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - - 0.000008*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - + SA_pls_int*d_endo - - + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - + - - 0.162969372349654 + + 0.162898568718522 - + 0.807533000000001 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - + 0.006 * BW / 73 - + - + V_slv - + - + V>0 ? M/V : 0 - - + + - + V>0 ? M/V : 0 - - + + - + V_slv - + - + V>0 ? M/V : 0 - - + + - + V>0 ? M/V : 0 - - + + - + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - + + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V - - - + + + - + -(Q*(1-HCT)*C_pls) - - - + + + - + Q*(1-HCT)*C_pls - - - + + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V - - - + + + - - -(Q*HCT*C_bc) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - + + + + + + + - - Q*HCT*C_bc + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - + + + + + + + - - P_int_cell * SA + + HCT * A_to_V_bc * 0.6 * V * f_vas - - + + + + - - P * P_cell_int_factor + + -(Q*HCT*C_bc) - - + + + - - P_cell_int * SA + + Q*HCT*C_bc - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - + + + + - - fu/K_cell_pls + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - + + + + + + - - P * P_int_cell_factor + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - + + + + + + - - fu/K_int_pls + + k * f_vas_org * V_org - - + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + P_cell_int * SA - - - - - - + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + fu/K_cell_pls - - - - - - + + - - (V_bon * 1000 / 28.2)^0.75 * 10 * 1E2 + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - + + + + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + P_int_cell * SA - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + P * P_cell_int_factor - - - - - - + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + P * P_int_cell_factor - - - - - - + + - - k * f_vas_org * V_org + + fu/K_int_pls - - - + + - - -(Q*(1-HCT)*C_pls) + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - + + + + + + - - Q*(1-HCT)*C_pls + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - + + + + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (V_bon * 1000 / 28.2)^0.75 * 10 * 1E2 - - - - - - - + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(Q*(1-HCT)*C_pls) - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + Q*(1-HCT)*C_pls - - - - + + + - - P/2 + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - + + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + P/2 - - - - + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - + + + - - fu/K_cell_pls + + -(Q*(1-HCT)*C_pls) - - + + + - - P * P_int_cell_factor + + Q*(1-HCT)*C_pls - - + + + - - P * P_cell_int_factor + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + + + + + + + + + + P_cell_int * SA - - + + - + P_int_cell * SA - - + + - - P_cell_int * SA + + P * P_cell_int_factor - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P * P_int_cell_factor + + + + + + + fu/K_cell_pls - - - - - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_brn * 1000 / 1.671)^0.75 * 0.0006 * 1E2 - + - + -(Q*(1-HCT)*C_pls) - - - + + + - + Q*(1-HCT)*C_pls - - - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - - + + + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + fu/K_cell_pls - - - - - - - + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + P_cell_int * SA - - - - + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + P_int_cell * SA - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + P * P_cell_int_factor - - - - - - + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + P * P_int_cell_factor - - - - - - + + - - k * f_vas_org * V_org + + fu/K_int_pls - - - + + - - -(Q*(1-HCT)*C_pls) + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - + + + + + + - - Q*(1-HCT)*C_pls + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - + + + + + + - - P * P_int_cell_factor + + (V_fat * 1000 / 14.2)^0.75 * 5 * 1E2 - - + - - P_int_cell * SA + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - + + + + - - P_cell_int * SA + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - + + + + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - - fu/K_cell_pls + + k * f_vas_org * V_org - - + + + - - P * P_cell_int_factor + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - + + + + + + + - - fu/K_int_pls + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - + + + + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - - + + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + -(Q*HCT*C_bc) - - - - - - + + + - - (V_fat * 1000 / 14.2)^0.75 * 5 * 1E2 + + Q*HCT*C_bc - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + -(Q*(1-HCT)*C_pls) - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + Q*(1-HCT)*C_pls - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - - -(Q*HCT*C_bc) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - + + + + + + - - Q*HCT*C_bc + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - + + + + + + - + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + fu/K_cell_pls - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - - P * P_int_cell_factor + + P_cell_int * SA - - + + - - P * P_cell_int_factor + + P_int_cell * SA - - + + - - P_int_cell * SA + + P * P_cell_int_factor - - + + - - P_cell_int * SA + + P * P_int_cell_factor - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_tes * 1000 / 2.5)^0.75 * 2 * 1E2 - + - + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + -(Q*(1-HCT)*C_pls) - - - + + + - + Q*(1-HCT)*C_pls - - - + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + P_cell_int * SA - - - - - - - + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - - + + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + fu/K_cell_pls - - - - + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + P * P_int_cell_factor - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - - - - - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - - - - - - k * f_vas_org * V_org - - - - - - - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + P * P_cell_int_factor - - - - - - - + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + P_int_cell * SA - - - - - - - + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + fu/K_int_pls - - - - + + - - -(Q*(1-HCT)*C_pls) + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - + + + + + + - - Q*(1-HCT)*C_pls + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - + + + + + + - - -(Q*HCT*C_bc) + + (V_hrt * 1000 / 1.2)^0.75 * 7.54 * 1E2 - - - + - - Q*HCT*C_bc + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - + + + + + + + - - P * P_int_cell_factor + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - + + + + + + + - - P * P_cell_int_factor + + HCT * A_to_V_bc * 0.6 * V * f_vas - - + + + + - - P_int_cell * SA + + -(Q*HCT*C_bc) - - + + + - - P_cell_int * SA + + Q*HCT*C_bc - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + Q*(1-HCT)*C_pls - - - - - - + + + - - fu/K_cell_pls + + -(MassTransferMucosaToPvePlasmaRate) - - + - - fu/K_int_pls + + MassTransferMucosaToPvePlasmaRate - - + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - - - + + 0 - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + (1-F1)*(1-F2)*(1-F3) - - - - - - + + + - - (V_hrt * 1000 / 1.2)^0.75 * 7.54 * 1E2 + + P_1 - + - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - - - - - - + + + + - - 0 - - - P_1 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - + + + + - - -(DrugAbsorptionLumenToMucosaRate) + + F1*F2*F3 - + + + - - DrugAbsorptionLumenToMucosaRate + + (1-F1)*F2*F3 - + + + - - DrugAbsorptionLumenToMucosaRate + + F1*(1-F2)*F3 - + + + - + F1*F2*(1-F3) - - - - - - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - - - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + (1-F1)*(1-F2)*F3 - - - - - - - - - - - - - + + + - - K_cell_pls + + (1-F1)*F2*(1-F3) - + + + - - K_water_cell + + F1*(1-F2)*(1-F3) - + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + K_water_cell - - - - + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + F1*F2*F3 - - - - - - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - + + + - - (1-F1)*F2*(1-F3) + + (1-F1)*F2*F3 - - - + + + - - (1-F1)*(1-F2)*F3 + + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - - F1*(1-F2)*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - - (1-F1)*F2*F3 + + (1-F1)*F2*(1-F3) - - - + + + - - (1-F1)*F2*F3 + + F1*(1-F2)*(1-F3) - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - F1*(1-F2)*F3 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + - - F1*(1-F2)*(1-F3) + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - (1-F1)*F2*(1-F3) + + DrugAbsorptionLumenToMucosaRate - - - + - - (1-F1)*(1-F2)*F3 + + DrugAbsorptionLumenToMucosaRate - - - + - - F1*F2*F3 + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + - + 0 - - F1*(1-F2)*(1-F3) - - - - - - - + P_1 - - - - - (1-F1)*(1-F2)*(1-F3) - - - - + - + -(DrugAbsorptionLumenToMucosaRate) - + - + DrugAbsorptionLumenToMucosaRate - + - + DrugAbsorptionLumenToMucosaRate - + - - Q*(1-HCT)*C_pls + + Q*HCT*C_bc - - - + + + - - -(MassTransferMucosaToPvePlasmaRate) + + -(MassTransferMucosaToPveBCRate) - + - - MassTransferMucosaToPvePlasmaRate + + MassTransferMucosaToPveBCRate - + - - P * P_int_cell_factor + + K_water_cell - - + - - P * P_cell_int_factor + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - + + + + + + + - - P_int_cell * SA + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - + + + + + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - - + + + + - - fu/K_cell_pls + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - + + + + - - P_cell_int * SA + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - + + + + + + - - fu/K_int_pls + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - + + + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + k * f_vas_org * V_org - - - - - - + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + -(fu * TSspec * V_kid * C_kid_pls * Renal_aging_scaling_factor) - - - - - - + + + + + - - (V_kid * 1000 / 7)^0.75 * 1000 * 1E2 + + fu * TSspec * V_kid * C_kid_pls * Renal_aging_scaling_factor - + + + + + - - K_water_cell + + TS / V_kid - + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + -(fu * GFRspec*GFR_Fraction* Weight_Kidney * C_kid_pls) - - - - - - - + + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + fu * GFRspec*GFR_Fraction* Weight_Kidney * C_kid_pls - - - - - - - + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + -(Q*(1-HCT)*C_pls) - - - - + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + Q*(1-HCT)*C_pls - - - - + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + fu/K_cell_pls - - - - - - + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - - k * f_vas_org * V_org + + P * P_int_cell_factor - - - + + - - -(Q*(1-HCT)*C_pls) - - - - - - - - Q*(1-HCT)*C_pls - - - - - - - - -(Q*HCT*C_bc) - - - - - - - - Q*HCT*C_bc - - - - - - - - Q*HCT*C_bc - - - - - - - - -(MassTransferMucosaToPveBCRate) - - - - - - MassTransferMucosaToPveBCRate + + P * P_cell_int_factor - + + - - P_1 + + P_int_cell * SA - + + - - 0 - - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + P_cell_int * SA - - - - - - - - - - + + - - -(DrugAbsorptionLumenToMucosaRate) + + fu/K_int_pls - + + - - DrugAbsorptionLumenToMucosaRate + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - + + + + + + - - DrugAbsorptionLumenToMucosaRate + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - + + + + + + - - F1*F2*F3 + + (V_kid * 1000 / 7)^0.75 * 1000 * 1E2 - - - + - + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - - - - - 0 - - - P_1 - - + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - - - - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - - + + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - - - - - - - - - + + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - - - (1-F1)*F2*F3 + + F1*F2*F3 - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - F1*(1-F2)*(1-F3) + + F1*(1-F2)*F3 - - - + + + - - (1-F1)*F2*(1-F3) + + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - - - - F1*(1-F2)*F3 + + (1-F1)*F2*(1-F3) - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + F1*(1-F2)*(1-F3) - - - - + + + - - F1*F2*F3 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - + + 0 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*F2*F3 - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*F2*F3 - - - - + + + - - K_water_cell + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + K_cell_pls - + - - F1*F2*(1-F3) + + K_water_cell - - - + - - -(DrugAbsorptionLumenToMucosaRate) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - + + + + - - DrugAbsorptionLumenToMucosaRate + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - + + + + - - DrugAbsorptionLumenToMucosaRate + + P_1 - + - - Q*(1-HCT)*C_pls + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - -(MassTransferMucosaToPvePlasmaRate) + + DrugAbsorptionLumenToMucosaRate - + - - MassTransferMucosaToPvePlasmaRate + + DrugAbsorptionLumenToMucosaRate - + - - Q*HCT*C_bc + + 0 + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + - - -(MassTransferMucosaToPveBCRate) + + P_1 - + - - MassTransferMucosaToPveBCRate + + -(DrugAbsorptionLumenToMucosaRate) - + - - -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + DrugAbsorptionLumenToMucosaRate - - - - - + - - (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + DrugAbsorptionLumenToMucosaRate - - - - - + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - + MAbs_duo + MAbs_uje + MAbs_lje + MAbs_uil + MAbs_lil + MAbs_cae + MAbs_colasc + MAbs_coltrans + MAbs_coldesc + MAbs_colsigm + MAbs_rect - - - - - - - - - - - + + + + + + + + + + + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - - -(OralApplicationsEnabled ? w*Drug : 0) + + Q*(1-HCT)*C_pls - - - + + + - - OralApplicationsEnabled ? w*Drug : 0 + + -(MassTransferMucosaToPvePlasmaRate) - - - + - - -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + MassTransferMucosaToPvePlasmaRate - - - - - + - - (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + Q*HCT*C_bc - - - - - + + + - - -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + -(MassTransferMucosaToPveBCRate) - - - - - + - - (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + MassTransferMucosaToPveBCRate - - - - - + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - + + + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - - + + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - - + + + + + - - k * f_vas_org * V_org + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - + + + + + - - -(Q*HCT*C_bc) + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - + + + + + - - Q*HCT*C_bc + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - + + + + + - - -(Q*(1-HCT)*C_pls) + + -(OralApplicationsEnabled ? w*Drug : 0) - - - + + + - - Q*(1-HCT)*C_pls + + OralApplicationsEnabled ? w*Drug : 0 - - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P_cell_int * SA - - - - - - + + - - fu/K_cell_pls + + P * P_int_cell_factor - - + + - - P_cell_int * SA + + P * P_cell_int_factor - - + + - + P_int_cell * SA - - + + - - P * P_int_cell_factor + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - - P * P_cell_int_factor + + fu/K_cell_pls - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_sto * 1000 / 1.1)^0.75 * 1000 * 1E2 - + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + -(Q*HCT*C_bc) - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + Q*HCT*C_bc - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + (1-F1)*(1-F2)*F3 - - - - + + + - - P_1 + + (1-F1)*F2*(1-F3) - + + + - - 0 + + F1*(1-F2)*(1-F3) + + + + + - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + (1-F1)*(1-F2)*(1-F3) - - - - - - - - - - + + + - - -(DrugAbsorptionLumenToMucosaRate) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - + + + + - - DrugAbsorptionLumenToMucosaRate + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - + + + + - - DrugAbsorptionLumenToMucosaRate + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - + + + + - - (1-F1)*F2*F3 + + F1*F2*F3 - - - + + + - - F1*(1-F2)*(1-F3) + + (1-F1)*F2*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - - (1-F1)*(1-F2)*F3 + + F1*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - - - + + 0 - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + P_1 - - - - + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + F1*(1-F2)*F3 - - - - + + + - - F1*F2*F3 + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + - - (1-F1)*F2*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - - F1*(1-F2)*F3 + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + + + + - + F1*F2*(1-F3) - - - + + + - - (1-F1)*(1-F2)*F3 + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - (1-F1)*F2*(1-F3) + + + + + + + + + + + + + + + + + K_cell_pls - - - + - - P_1 + + K_water_cell - + - - 0 - - - (1-F1)*(1-F2)*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - F1*F2*F3 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - F1*(1-F2)*F3 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + F1*F2*F3 - - - - - - - - - - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + (1-F1)*F2*F3 - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + -(DrugAbsorptionLumenToMucosaRate) - - - - + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + DrugAbsorptionLumenToMucosaRate - - - - + - - K_water_cell + + DrugAbsorptionLumenToMucosaRate - + - - K_cell_pls + + -(Q*(1-HCT)*C_pls) - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + Q*(1-HCT)*C_pls - - - - - - - - - - - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - - - - - - - + + + + - - -(DrugAbsorptionLumenToMucosaRate) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - + + + + + + - - DrugAbsorptionLumenToMucosaRate + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - + + + + + + - - DrugAbsorptionLumenToMucosaRate + + k * f_vas_org * V_org - + + + - - Q*(1-HCT)*C_pls + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - + + + + + + + - - -(MassTransferMucosaToPvePlasmaRate) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - + + + + + + + - - MassTransferMucosaToPvePlasmaRate + + HCT * A_to_V_bc * 0.6 * V * f_vas - + + + + - + Q*HCT*C_bc - - - + + + - + -(MassTransferMucosaToPveBCRate) - + - + MassTransferMucosaToPveBCRate - + - - -((1-fractQ)*Q*(1-HCT)*C) + + Q*(1-HCT)*C_pls - - - - + + + - - (1-fractQ)*Q*(1-HCT)*C + + -(MassTransferMucosaToPvePlasmaRate) - - - - + - - P * P_cell_int_factor + + MassTransferMucosaToPvePlasmaRate - - + - - P_int_cell * SA + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - + + + + + + + + + + - - P_cell_int * SA + + 0 + + + P_1 - - + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + -(DrugAbsorptionLumenToMucosaRate) - - - - - - + - - fu/K_cell_pls + + DrugAbsorptionLumenToMucosaRate - - + - - P * P_int_cell_factor + + DrugAbsorptionLumenToMucosaRate - - + - - fu/K_int_pls + + Q*(1-HCT)*C_pls - - + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + -(MassTransferIntestineToMucosaPlasmaRate) - - - - - - + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + MassTransferIntestineToMucosaPlasmaRate - - - - - - + - - ((V_sin-V_Mucosa) * 1000 / 11.1)^0.75 * 1000 * 1E2 + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - + + + + + + + + + + - - Q*(1-HCT)*C_pls + + 0 + + + P_1 - - - + - - -(MassTransferIntestineToMucosaPlasmaRate) + + -(DrugAbsorptionLumenToMucosaRate) - + - - MassTransferIntestineToMucosaPlasmaRate + + DrugAbsorptionLumenToMucosaRate - + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + DrugAbsorptionLumenToMucosaRate - - - - + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + F1*(1-F2)*F3 - - - - - - + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + F1*F2*(1-F3) - - - - - - + + + - - k * f_vas_org * (V_org-V_Mucosa) + + (1-F1)*(1-F2)*F3 - - - - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (1-F1)*F2*(1-F3) - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + F1*(1-F2)*(1-F3) - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * (V-V_Mucosa) * f_vas + + (1-F1)*(1-F2)*(1-F3) - - - - - + + + - - Q*(1-HCT)*C_pls + + 0 + + + P_1 - - - + - - -(MassTransferIntestineToMucosaPlasmaRate) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - + + + + - - MassTransferIntestineToMucosaPlasmaRate + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - + + + + - - Q*HCT*C_bc + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + + + + - - -(MassTransferIntestineToMucosaBCRate) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - + + + + + + + + + + + + + - - MassTransferIntestineToMucosaBCRate + + K_cell_pls - + - - -((1-fractQ)*Q*HCT*C) + + K_water_cell - - - - + - - (1-fractQ)*Q*HCT*C + + (1-F1)*F2*F3 - - - - + + + - - Q*HCT*C_bc + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - -(MassTransferMucosaToPveBCRate) + + F1*F2*F3 - + + + - - MassTransferMucosaToPveBCRate + + F1*F2*F3 - + + + - - Q*(1-HCT)*C_pls + + (1-F1)*F2*F3 - - - + + + - - -(MassTransferMucosaToPvePlasmaRate) + + F1*(1-F2)*F3 - + + + - - MassTransferMucosaToPvePlasmaRate + + F1*F2*(1-F3) - + + + - - Q*HCT*C_bc + + (1-F1)*(1-F2)*F3 - - - + + + - - -(MassTransferIntestineToMucosaBCRate) + + (1-F1)*F2*(1-F3) - + + + - - MassTransferIntestineToMucosaBCRate + + F1*(1-F2)*(1-F3) - + + + - - Q*(1-HCT)*C_pls + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - + + + + - - MassTransferIntestineToMucosaPlasmaRate + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - + + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + -(DrugAbsorptionLumenToMucosaRate) - - - - - - - - - - - - - + - - K_cell_pls + + DrugAbsorptionLumenToMucosaRate - + - - K_water_cell + + DrugAbsorptionLumenToMucosaRate - + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + Q*HCT*C_bc - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + -(MassTransferIntestineToMucosaBCRate) - - - - + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + MassTransferIntestineToMucosaBCRate - - - - + - - F1*F2*F3 + + Q*HCT*C_bc - - - + + + - - (1-F1)*F2*F3 + + -(MassTransferIntestineToMucosaBCRate) - - - + - - F1*(1-F2)*F3 + + MassTransferIntestineToMucosaBCRate - - - + - - F1*F2*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - (1-F1)*(1-F2)*F3 + + -(MassTransferMucosaToPvePlasmaRate) - - - + - - (1-F1)*F2*(1-F3) + + MassTransferMucosaToPvePlasmaRate - - - + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - - - - F1*F2*(1-F3) + + Q*HCT*C_bc - - - + + + - - P_1 + + -(MassTransferMucosaToPveBCRate) - + - - 0 + + MassTransferMucosaToPveBCRate + + + - - (1-F1)*(1-F2)*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - F1*(1-F2)*(1-F3) + + -(MassTransferIntestineToMucosaPlasmaRate) - - - + - - F1*(1-F2)*(1-F3) + + MassTransferIntestineToMucosaPlasmaRate - - - + - - (1-F1)*(1-F2)*F3 + + Q*HCT*C_bc - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + -(MassTransferIntestineToMucosaBCRate) - - - + - - F1*(1-F2)*F3 + + MassTransferIntestineToMucosaBCRate - - - + - - (1-F1)*F2*F3 + + Q*(1-HCT)*C_pls - - - + + + - - F1*F2*F3 + + -(MassTransferIntestineToMucosaPlasmaRate) - - - + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + MassTransferIntestineToMucosaPlasmaRate - - - - + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + Q*HCT*C_bc - - - - + + + - - (1-F1)*F2*(1-F3) + + -(MassTransferIntestineToMucosaBCRate) - - - + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + MassTransferIntestineToMucosaBCRate - - - - - - - - - - - - - + - - -(DrugAbsorptionLumenToMucosaRate) + + Q*(1-HCT)*C_pls - + + + - - DrugAbsorptionLumenToMucosaRate + + -(MassTransferIntestineToMucosaPlasmaRate) - + - - DrugAbsorptionLumenToMucosaRate + + MassTransferIntestineToMucosaPlasmaRate - + - + Q*HCT*C_bc - - - + + + - + -(MassTransferIntestineToMucosaBCRate) - + - + MassTransferIntestineToMucosaBCRate - + - - P_1 + + Q*(1-HCT)*C_pls - + + + - - 0 - - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + -(MassTransferIntestineToMucosaPlasmaRate) - - - - - - - - - - + - - -(DrugAbsorptionLumenToMucosaRate) + + MassTransferIntestineToMucosaPlasmaRate - + - - DrugAbsorptionLumenToMucosaRate + + -((1-fractQ)*Q*HCT*C) - + + + + - - DrugAbsorptionLumenToMucosaRate + + (1-fractQ)*Q*HCT*C - + + + + - - Q*HCT*C_bc + + P * P_int_cell_factor - - - + + - - -(MassTransferIntestineToMucosaBCRate) + + P * P_cell_int_factor - + + - - MassTransferIntestineToMucosaBCRate + + P_int_cell * SA - + + - - Q*(1-HCT)*C_pls + + P_cell_int * SA - - - + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - + + + + + + - - MassTransferIntestineToMucosaPlasmaRate + + fu/K_cell_pls - + + - - Q*HCT*C_bc + + fu/K_int_pls - - - + + - - -(MassTransferIntestineToMucosaBCRate) + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - + + + + + + - - MassTransferIntestineToMucosaBCRate + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - + + + + + + - - Q*(1-HCT)*C_pls + + ((V_sin-V_Mucosa) * 1000 / 11.1)^0.75 * 1000 * 1E2 - - - + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - + + + + + + + - - MassTransferIntestineToMucosaPlasmaRate + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - + + + + + + + - - Q*(1-HCT)*C_pls + + HCT * A_to_V_bc * 0.6 * (V-V_Mucosa) * f_vas - - - + + + + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - + + + + - - MassTransferIntestineToMucosaPlasmaRate + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - + + + + + + - - Q*(1-HCT)*C_pls + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - + + + + + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + k * f_vas_org * (V_org-V_Mucosa) - + + + + - - MassTransferIntestineToMucosaPlasmaRate + + -((1-fractQ)*Q*(1-HCT)*C) - + + + + - - Q*HCT*C_bc + + (1-fractQ)*Q*(1-HCT)*C - - - + + + + - - -(MassTransferIntestineToMucosaBCRate) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - + + + + + + - - MassTransferIntestineToMucosaBCRate + + P * P_int_cell_factor - + + - - Q*(1-HCT)*C_pls + + P * P_cell_int_factor - - - + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + P_int_cell * SA - + + - - MassTransferIntestineToMucosaPlasmaRate + + P_cell_int * SA - + + - - Q*HCT*C_bc + + fu/K_cell_pls - - - + + - - -(MassTransferIntestineToMucosaBCRate) + + fu/K_int_pls - + + - - MassTransferIntestineToMucosaBCRate + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - + + + + + + - - Q*(1-HCT)*C_pls + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - + + + + + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + ((V_lin-V_Mucosa) * 1000 / 11.1)^0.75 * 1000 * 1E2 - + + - - MassTransferIntestineToMucosaPlasmaRate + + -((1-fractQ)*Q*HCT*C) - + + + + - - Q*HCT*C_bc + + (1-fractQ)*Q*HCT*C - - - + + + + - - -(MassTransferIntestineToMucosaBCRate) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - + + + + + + + - - MassTransferIntestineToMucosaBCRate + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - + + + + + + + - - Q*HCT*C_bc + + HCT * A_to_V_bc * 0.6 * (V-V_Mucosa) * f_vas - - - + + + + + - - -(MassTransferIntestineToMucosaBCRate) + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - + + + + - - MassTransferIntestineToMucosaBCRate + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - + + + + + + - - Q*(1-HCT)*C_pls + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - + + + + + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + k * f_vas_org * (V_org-V_Mucosa) - + + + + - - MassTransferIntestineToMucosaPlasmaRate + + -((1-fractQ)*Q*(1-HCT)*C) - + + + + - + + (1-fractQ)*Q*(1-HCT)*C + + + + + + + + Q*HCT*C_bc - - - + + + - + -(MassTransferIntestineToMucosaBCRate) - + - + MassTransferIntestineToMucosaBCRate - + - + Q*(1-HCT)*C_pls - - - + + + - + -(MassTransferIntestineToMucosaPlasmaRate) - + - + MassTransferIntestineToMucosaPlasmaRate - + - + Q*HCT*C_bc - - - + + + - + -(MassTransferIntestineToMucosaBCRate) - + - + MassTransferIntestineToMucosaBCRate - + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + Q*HCT*C_bc - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(MassTransferIntestineToMucosaBCRate) - - - - - - - + - - HCT * A_to_V_bc * 0.6 * (V-V_Mucosa) * f_vas + + MassTransferIntestineToMucosaBCRate - - - - - + - - P * P_int_cell_factor + + Q*(1-HCT)*C_pls - - + + + - - P * P_cell_int_factor + + -(MassTransferIntestineToMucosaPlasmaRate) - - + - - P_int_cell * SA + + MassTransferIntestineToMucosaPlasmaRate - - + - - P_cell_int * SA + + Q*HCT*C_bc - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + -(MassTransferIntestineToMucosaBCRate) - - - - - - + - - fu/K_cell_pls + + MassTransferIntestineToMucosaBCRate - - + - - fu/K_int_pls + + Q*(1-HCT)*C_pls - - + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + -(MassTransferIntestineToMucosaPlasmaRate) - - - - - - + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + MassTransferIntestineToMucosaPlasmaRate - - - - - - + - - ((V_lin-V_Mucosa) * 1000 / 11.1)^0.75 * 1000 * 1E2 + + Q*HCT*C_bc - - + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + -(MassTransferIntestineToMucosaBCRate) - - - - + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + MassTransferIntestineToMucosaBCRate - - - - - - + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + Q*(1-HCT)*C_pls - - - - - - + + + - - k * f_vas_org * (V_org-V_Mucosa) + + -(MassTransferIntestineToMucosaPlasmaRate) - - - - + - - -((1-fractQ)*Q*(1-HCT)*C) + + MassTransferIntestineToMucosaPlasmaRate - - - - + - - (1-fractQ)*Q*(1-HCT)*C + + Q*(1-HCT)*C_pls - - - - + + + - - -((1-fractQ)*Q*HCT*C) + + -(MassTransferIntestineToMucosaPlasmaRate) - - - - + - - (1-fractQ)*Q*HCT*C + + MassTransferIntestineToMucosaPlasmaRate - - - - + - - k * f_vas_org * V_org + + Q*(1-HCT)*C_pls - - - + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + -(MassTransferIntestineToMucosaPlasmaRate) - - - - + - - (V_liv * 1000 / 10)^0.75 * 82 * 1E2 + + MassTransferIntestineToMucosaPlasmaRate - + - - -(EHC_Active ? ln(2) / EHC_Halftime * M * EHC_EjectionFraction : 0) + + Q*HCT*C_bc - - - - + + + - - EHC_Active ? ln(2) / EHC_Halftime * M * EHC_EjectionFraction : 0 + + -(MassTransferIntestineToMucosaBCRate) - - - - + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + MassTransferIntestineToMucosaBCRate - - - - + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + -(EHC_Active ? ln(2) / EHC_Halftime * M * EHC_EjectionFraction : 0) - - - - - - + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + EHC_Active ? ln(2) / EHC_Halftime * M * EHC_EjectionFraction : 0 - - - - - - + + + + - - SA_pls_int * (IsLiverZonated? f_periportal : 1) + + k * f_vas_org * V_org - - - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - - - + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + (V_liv * 1000 / 10)^0.75 * 82 * 1E2 - - - - - - - + - - SA_pls_bc * (IsLiverZonated? f_periportal : 1) + + fu/K_cell_pls - - - + + - - P * P_int_cell_factor + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - - P * P_cell_int_factor + + P_cell_int * SA - - + + - + P_int_cell * SA - - - - - - P_cell_int * SA - - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P * P_cell_int_factor - - - - - - + + - - fu/K_cell_pls + + P * P_int_cell_factor - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + SA_int_cell * (IsLiverZonated? f_periportal : 1) - - - - - - - P * P_int_cell_factor - - - - - - - P * P_cell_int_factor - - - + + + - - P_cell_int * SA - - - - - - - fu/K_cell_pls + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - + + + + + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - + + + + + + + - - P_int_cell * SA + + SA_pls_bc * (IsLiverZonated? f_periportal : 1) - - + + + - - fu/K_int_pls + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - - SA_int_cell * (IsLiverZonated? 1-f_periportal : 0) + + SA_pls_int * (IsLiverZonated? f_periportal : 1) - - - + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + SA_pls_int * (IsLiverZonated? 1-f_periportal : 0) - - - + + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + SA_pls_bc * (IsLiverZonated? 1-f_periportal : 0) - - - + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + P * P_int_cell_factor - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + P_cell_int * SA - - - - - - + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + P * P_cell_int_factor - - - - - - + + - - k * f_vas_org * V_org + + P_int_cell * SA - - - + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - - + + + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + fu/K_cell_pls - - - - - - - + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + fu/K_int_pls - - - - + + - + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + SA_int_cell * (IsLiverZonated? 1-f_periportal : 0) + + + + + + + -(Q*(1-HCT)*C_pls) - - - + + + - + Q*(1-HCT)*C_pls - - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - + + + + - - fu/K_cell_pls + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - + + + + + + - + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + P * P_int_cell_factor - - + + - + P * P_cell_int_factor - - + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + - + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + + + + + + + + + + fu/K_cell_pls + + + + + + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_lng * 1000 / 2.2)^0.75 * 0.096 * 1E2 - + - + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + -(Q*(1-HCT)*C_pls) - - - - + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + Q*(1-HCT)*C_pls - - - - - - + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - + + + + + + + - - k * f_vas_org * V_org + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - + + + + + + + - - -(Q*HCT*C_bc) + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - + + + + - - Q*HCT*C_bc + + -(Q*HCT*C_bc) - - - + + + - - P * P_int_cell_factor + + Q*HCT*C_bc - - + + + - - P * P_cell_int_factor + + P_int_cell * SA - - + + - - P_int_cell * SA + + P * P_cell_int_factor - - + + - + P_cell_int * SA - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - + fu/K_cell_pls - - + + - + + P * P_int_cell_factor + + + + + + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_mus * 1000 / 110.1)^0.75 * 7.54 * 1E2 - - - - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - - + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - + + + + + + - - -(Q*(1-HCT)*C_pls) + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - + + + + + + - - Q*(1-HCT)*C_pls + + k * f_vas_org * V_org - - - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - - + + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - + + + + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + k * f_vas_org * V_org - - - - + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + -(Q*(1-HCT)*C_pls) - - - - - - + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + Q*(1-HCT)*C_pls - - - - - - + + + - - k * f_vas_org * V_org + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - + + + + + + + - - -(Q*(1-HCT)*C_pls) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - + + + + + + + - - Q*(1-HCT)*C_pls + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - + + + + - - P_cell_int * SA + + P * P_int_cell_factor - - + + - - P * P_int_cell_factor + + P * P_cell_int_factor - - + + - + P_int_cell * SA - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - + fu/K_cell_pls - - + + - - P * P_cell_int_factor + + P_cell_int * SA - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_pan * 1000 / 1.3)^0.75 * 1000 * 1E2 - + - + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - + + + - + Q*(1-HCT)*C_pls - - - + + + - + -(MassTransferMucosaToPvePlasmaRate) - + - + MassTransferMucosaToPvePlasmaRate - + - + Q*HCT*C_bc - - - + + + - + -(MassTransferMucosaToPveBCRate) - + - + MassTransferMucosaToPveBCRate - + - - 0 - - - 0 - - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - - - - - - + + + + - - F1*(1-F2)*(1-F3) + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + + + + - - (1-F1)*(1-F2)*(1-F3) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + - - 0 - - - P_1 + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - + + + + + + + + + + + + + - - (1-F1)*(1-F2)*F3 + + K_cell_pls - - - + - - F1*F2*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - F1*F2*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + F1*F2*F3 - - - - - - - - - - - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + (1-F1)*F2*F3 - - - - - - - - - - - - - - - - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - - - K_cell_pls - - - - - - K_water_cell - - - - - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - - - - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - - - - - - F1*F2*F3 - - - - - - - - (1-F1)*F2*(1-F3) + + F1*(1-F2)*F3 - - - + + + - - F1*(1-F2)*F3 + + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + K_water_cell - - - - + - - F1*F2*F3 + + (1-F1)*F2*F3 - - - + + + - - (1-F1)*F2*F3 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - + F1*(1-F2)*F3 - - - + + + - - (1-F1)*F2*F3 + + F1*F2*(1-F3) - - - + + + - - -(DrugAbsorptionLumenToMucosaRate) + + (1-F1)*(1-F2)*F3 - + + + - - DrugAbsorptionLumenToMucosaRate + + (1-F1)*F2*(1-F3) - + + + - - DrugAbsorptionLumenToMucosaRate + + F1*(1-F2)*(1-F3) - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (1-F1)*(1-F2)*(1-F3) - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - - - + + 0 - - HCT * A_to_V_bc * 0.6 * V + + P_1 - - - + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + F1*F2*F3 - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(DrugAbsorptionLumenToMucosaRate) - - - - - - - + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + DrugAbsorptionLumenToMucosaRate - - - - + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + DrugAbsorptionLumenToMucosaRate - - - - + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - - - - + + + + + + + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - - - + + 0 - - k * f_vas_org * V_org + + 0 + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - + + + + + + + - - -(Q*HCT*C_bc) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - + + + + + + + - - Q*HCT*C_bc + + HCT * A_to_V_bc * 0.6 * V - - - + + + - - -(Q*(1-HCT)*C_pls) + + -(Q*HCT*C_bc) - - - + + + - - Q*(1-HCT)*C_pls + + Q*HCT*C_bc - - - + + + - - fu/K_cell_pls + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - + P * P_int_cell_factor - - + + - + P * P_cell_int_factor - - + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + fu/K_cell_pls - - - - - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_skn * 1000 / 43.4)^0.75 * 0.12 * 1E2 - + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - + -(Q*(1-HCT)*C_pls) - - - + + + - + Q*(1-HCT)*C_pls - - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + -(Q*HCT*C_bc) - - - - - - + + + - - fu/K_cell_pls + + Q*HCT*C_bc - - + + + - - P * P_int_cell_factor + + P_cell_int * SA + + + + + + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + + + + + + + + + + fu/K_cell_pls - - + + - + P * P_cell_int_factor - - + + - - P_int_cell * SA + + P * P_int_cell_factor - - + + - - P_cell_int * SA + + P_int_cell * SA - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_spl * 1000 / 1.3)^0.75 * 1000 * 1E2 - + - - -(Q*HCT*C_bc) + + -(Q*(1-HCT)*C_pls) - - - + + + - - Q*HCT*C_bc + + Q*(1-HCT)*C_pls - - - + + + - + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + R * fu - - + + - + 1 - - - - - + + + + + - + -(fu * (C_pls_art - C_slv / K_slv_pls) * Q_slv) - - - - - + + + + + - + fu * (C_pls_art - C_slv / K_slv_pls) * Q_slv - - - - - + + + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - + + fu/K_cell_pls + + + + + + P * P_int_cell_factor * P_int_scalefactor - - - + + + - + P * P_cell_int_factor * P_int_scalefactor - - - + + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - - - - - fu/K_cell_pls - - - + + + + + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - + P * P_int_cell_factor * P_int_scalefactor - - - + + + - + P * P_cell_int_factor * P_int_scalefactor - - - - - - - P_int_cell * SA - - - + + + - + P_cell_int * SA - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - + fu/K_cell_pls - - + + - + + P_int_cell * SA + + + + + + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - - P * P_cell_int_factor * P_int_scalefactor + + P * P_int_cell_factor * P_int_scalefactor - - - + + + - - P * P_int_cell_factor * P_int_scalefactor + + P * P_cell_int_factor * P_int_scalefactor - - - + + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + fu/K_cell_pls - - - - - - + + - - fu/K_cell_pls + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + P_int_cell * SA - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + P_cell_int * SA - - - - - - + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - - k * f_vas_org * V_org + + fu/K_cell_pls - - - + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + P * P_int_cell_factor * P_int_scalefactor - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + P * P_cell_int_factor * P_int_scalefactor - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor - - - - + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + P * P_int_cell_factor * P_int_scalefactor - - - + + + - + P * P_cell_int_factor * P_int_scalefactor - - - + + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + fu/K_cell_pls - - - - - - + + - - fu/K_cell_pls + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - - + + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - + + + + + + + + + + k * f_vas_org * V_org + + + + - + P * P_int_cell_factor * P_int_scalefactor - - - + + + - + P * P_cell_int_factor * P_int_scalefactor - - - + + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - + fu/K_cell_pls - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - - - - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - + + + + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - + + + + + + + - - k * f_vas_org * V_org + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - + + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - P * P_cell_int_factor * P_int_scalefactor + + P_cell_int * SA - - - + + - - fu/K_cell_pls + + P * P_int_cell_factor * P_int_scalefactor - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P_int_cell * SA - - - - - - + + - - P_int_cell * SA + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - - P * P_int_cell_factor * P_int_scalefactor + + fu/K_cell_pls - - - + + - - P_cell_int * SA + + P * P_cell_int_factor * P_int_scalefactor - - + + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - - + + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org - - - - + + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - - fu/K_cell_pls + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - + + + + + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - + + + + + + + - - P_cell_int * SA + + HCT * A_to_V_bc * 0.6 * V * f_vas - - + + + + - - P_int_cell * SA + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - + + + + - + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + P * P_int_cell_factor * P_int_scalefactor - - - + + + - + P * P_cell_int_factor * P_int_scalefactor - - - + + + - - fu/K_int_pls + + P_int_cell * SA - - + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + P_cell_int * SA - - - - - - + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - - Aeff / MicrovilliFactor + + fu/K_cell_pls - - + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + fu/K_int_pls - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - - k * f_vas_org * V_org + + Aeff / MicrovilliFactor - - - + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - fu/K_cell_pls - - - - - - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - + + + + + + + - - P_cell_int * SA + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - + + + + + + + - - P_int_cell * SA + + HCT * A_to_V_bc * 0.6 * V * f_vas - - + + + + - + P * P_int_cell_factor * P_int_scalefactor - - - + + + - + P * P_cell_int_factor * P_int_scalefactor - - - + + + - - fu/K_int_pls + + P_int_cell * SA - - + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + P_cell_int * SA - - - - - - + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - - Aeff / MicrovilliFactor + + fu/K_cell_pls - - + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + fu/K_int_pls - - - - - - - + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - - + + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - + + + + + + - - fu/K_cell_pls + + Aeff / MicrovilliFactor - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P_cell_int * SA - - - - - - + + - - P_cell_int * SA + + P * P_cell_int_factor * P_int_scalefactor - - + + + - + P_int_cell * SA - - + + - - P * P_cell_int_factor * P_int_scalefactor + + P * P_int_cell_factor * P_int_scalefactor - - - + + + - - P * P_int_cell_factor * P_int_scalefactor + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - + + + + + + - + + fu/K_cell_pls + + + + + + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - P_cell_int * SA + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - + + + + - - fu/K_cell_pls + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - + + + + + + - - P_int_cell * SA + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org - - + + + + + + + fu/K_cell_pls + + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + P * P_cell_int_factor * P_int_scalefactor - - - + + + - - P * P_int_cell_factor * P_int_scalefactor + + P_int_cell * SA - - - + + - + + P_cell_int * SA + + + + + + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + -(Q*(1-HCT)*C_pls) - - - - + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + Q*(1-HCT)*C_pls - - - - - - + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + -(Q*(1-HCT)*C_pls) - - - - - - + + + - - k * f_vas_org * V_org + + Q*(1-HCT)*C_pls - - - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + -(Q*(1-HCT)*C_pls) - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + Q*(1-HCT)*C_pls - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + F1*(1-F2)*(1-F3) - - - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + K_water_cell - - - - - - + - - fu/K_cell_pls + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - + + + + - - P_int_cell * SA + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - + + + + - - P_cell_int * SA + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - + + + + - - P * P_cell_int_factor * P_int_scalefactor + + F1*F2*F3 - - - + + + - - P * P_int_cell_factor * P_int_scalefactor + + (1-F1)*F2*F3 - - - + + + - - fu/K_int_pls + + F1*(1-F2)*F3 - - + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + F1*F2*(1-F3) - - - - - - + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + (1-F1)*(1-F2)*F3 - - - - - - + + + - - Aeff / MicrovilliFactor + + (1-F1)*F2*(1-F3) - - + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - - - + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - - + + + + - - k * f_vas_org * V_org + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - Q*(1-HCT)*C_pls + + F1*F2*F3 - - - + + + - - -(MassTransferMucosaToPvePlasmaRate) + + (1-F1)*F2*F3 - + + + - - MassTransferMucosaToPvePlasmaRate + + F1*(1-F2)*F3 - + + + - - Q*HCT*C_bc + + (1-F1)*(1-F2)*F3 - - - + + + - - -(MassTransferMucosaToPveBCRate) + + K_cell_pls - + - - MassTransferMucosaToPveBCRate + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - + + + + + + + + + + + + + - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - 0 - - - 0 - - - 0 - - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + + + + + + + + + (1-F1)*F2*(1-F3) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + F1*F2*(1-F3) - - - - + + + - - F1*F2*F3 + + F1*(1-F2)*(1-F3) - - - + + + - - (1-F1)*F2*F3 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - F1*(1-F2)*F3 - - - - - + + 0 - - F1*F2*(1-F3) + + P_1 - - - + - - (1-F1)*(1-F2)*F3 + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - (1-F1)*F2*(1-F3) + + DrugAbsorptionLumenToMucosaRate - - - + - - (1-F1)*(1-F2)*(1-F3) + + DrugAbsorptionLumenToMucosaRate - - - + - - (1-F1)*(1-F2)*(1-F3) + + -(Q*(1-HCT)*C_pls) - - - + + + - - F1*(1-F2)*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - P_1 + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - + + + + + + + + + + - - F1*(1-F2)*(1-F3) - - - - - + + 0 - - K_cell_pls + + P_1 - + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - - - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + -(DrugAbsorptionLumenToMucosaRate) - - - - + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - - - K_water_cell + + DrugAbsorptionLumenToMucosaRate - + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + DrugAbsorptionLumenToMucosaRate - - - - + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + -(Q*(1-HCT)*C_pls) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + Q*(1-HCT)*C_pls - - - - + + + - - F1*F2*F3 + + -(Q*(1-HCT)*C_pls) - - - + + + - - (1-F1)*F2*F3 + + Q*(1-HCT)*C_pls - - - + + + - - F1*(1-F2)*F3 + + -(Q*(1-HCT)*C_pls) - - - + + + - - F1*F2*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - (1-F1)*(1-F2)*F3 + + -(Q*(1-HCT)*C_pls) - - - + + + - - (1-F1)*F2*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - - - -(DrugAbsorptionLumenToMucosaRate) + + -(Q*(1-HCT)*C_pls) - + + + - - DrugAbsorptionLumenToMucosaRate + + Q*(1-HCT)*C_pls - + + + - - DrugAbsorptionLumenToMucosaRate + + -(Q*(1-HCT)*C_pls) - + + + - + Q*(1-HCT)*C_pls - - - + + + - - -(MassTransferMucosaToPvePlasmaRate) + + -(Q*(1-HCT)*C_pls) - + + + - - MassTransferMucosaToPvePlasmaRate + + Q*(1-HCT)*C_pls - + + + - + Q*HCT*C_bc - - - + + + - + -(MassTransferMucosaToPveBCRate) - + - + MassTransferMucosaToPveBCRate - + - - P_1 + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - + + + + + + + + + + - + 0 - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - - - - - - - - - - + + 0 - - -(DrugAbsorptionLumenToMucosaRate) + + Q*(1-HCT)*C_pls - + + + - - DrugAbsorptionLumenToMucosaRate + + -(MassTransferMucosaToPvePlasmaRate) - + - - DrugAbsorptionLumenToMucosaRate + + MassTransferMucosaToPvePlasmaRate - + - - -(Q*(1-HCT)*C_pls) + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + - - Q*(1-HCT)*C_pls - - - - - + + 0 - - -(Q*(1-HCT)*C_pls) - - - - - + + 0 - - Q*(1-HCT)*C_pls + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + + + + - - -(Q*(1-HCT)*C_pls) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - Q*(1-HCT)*C_pls + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + - - -(Q*(1-HCT)*C_pls) + + K_cell_pls - - - + - - Q*(1-HCT)*C_pls + + K_water_cell - - - + - - -(Q*(1-HCT)*C_pls) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - Q*(1-HCT)*C_pls + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - -(Q*(1-HCT)*C_pls) + + (1-F1)*F2*F3 - - - + + + - - Q*(1-HCT)*C_pls + + F1*F2*F3 - - - + + + - - -(Q*(1-HCT)*C_pls) + + (1-F1)*F2*F3 - - - + + + - - Q*(1-HCT)*C_pls + + F1*(1-F2)*F3 - - - + + + - - -(Q*(1-HCT)*C_pls) + + F1*F2*(1-F3) - - - + + + - - Q*(1-HCT)*C_pls + + (1-F1)*(1-F2)*F3 - - - + + + - - -(Q*(1-HCT)*C_pls) + + (1-F1)*F2*(1-F3) - - - + + + - - Q*(1-HCT)*C_pls + + F1*(1-F2)*(1-F3) - - - + + + - - -(Q*(1-HCT)*C_pls) + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - Q*(1-HCT)*C_pls + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - -(Q*(1-HCT)*C_pls) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - Q*(1-HCT)*C_pls + + F1*F2*F3 - - - + + + - - -(Q*(1-HCT)*C_pls) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - Q*(1-HCT)*C_pls + + F1*(1-F2)*F3 - - - + + + - - -(Q*HCT*C_bc) + + F1*F2*(1-F3) - - - + + + - - Q*HCT*C_bc + + (1-F1)*(1-F2)*F3 - - - + + + - - -(Q*HCT*C_bc) + + (1-F1)*F2*(1-F3) - - - + + + - - Q*HCT*C_bc + + F1*(1-F2)*(1-F3) - - - + + + - - -(Q*HCT*C_bc) + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - Q*HCT*C_bc - - - - - + + 0 - - -(Q*HCT*C_bc) + + P_1 - - - + - - Q*HCT*C_bc + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - -(Q*HCT*C_bc) + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - Q*HCT*C_bc + + DrugAbsorptionLumenToMucosaRate - - - + - - -(Q*HCT*C_bc) + + DrugAbsorptionLumenToMucosaRate - - - + - + Q*HCT*C_bc - - - + + + - - -(Q*(1-HCT)*C_pls) + + -(MassTransferMucosaToPveBCRate) - - - + - - Q*(1-HCT)*C_pls + + MassTransferMucosaToPveBCRate - - - + - - K_cell_pls + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - + + + + + + + + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - + + 0 - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + 0 + + + Q*(1-HCT)*C_pls - - - - - - - - - - - - - + + + - - K_water_cell + + -(MassTransferMucosaToPvePlasmaRate) - + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + MassTransferMucosaToPvePlasmaRate - - - - - - - - - - - - - + - - (1-F1)*F2*F3 + + Q*HCT*C_bc - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + -(MassTransferMucosaToPveBCRate) - - - - + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + MassTransferMucosaToPveBCRate - - - - + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + Q*(1-HCT)*C_pls - - - - + + + - - F1*F2*F3 + + -(MassTransferMucosaToPvePlasmaRate) - - - + - - (1-F1)*F2*F3 + + MassTransferMucosaToPvePlasmaRate - - - + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - - - + + 0 - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + P_1 - - - - + - - (1-F1)*(1-F2)*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - - 0 - - - F1*F2*F3 + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + + + + - - F1*(1-F2)*(1-F3) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + - - (1-F1)*F2*(1-F3) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + - - (1-F1)*(1-F2)*F3 + + K_cell_pls - - - + - - F1*F2*(1-F3) + + K_water_cell - - - + - - F1*(1-F2)*F3 + + (1-F1)*F2*F3 - - - + + + - - P_1 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - + + + + - - -(DrugAbsorptionLumenToMucosaRate) + + F1*F2*F3 - + + + - - DrugAbsorptionLumenToMucosaRate + + F1*F2*F3 - + + + - - DrugAbsorptionLumenToMucosaRate + + (1-F1)*F2*F3 - + + + - - Q*(1-HCT)*C_pls + + F1*(1-F2)*F3 - - - + + + - - -(MassTransferMucosaToPvePlasmaRate) + + F1*F2*(1-F3) - + + + - - MassTransferMucosaToPvePlasmaRate + + (1-F1)*(1-F2)*F3 - + + + - - Q*HCT*C_bc + + (1-F1)*F2*(1-F3) - - - + + + - - -(MassTransferMucosaToPveBCRate) + + F1*(1-F2)*(1-F3) - + + + - - MassTransferMucosaToPveBCRate + + (1-F1)*(1-F2)*(1-F3) - + + + - - -(Q*HCT*C_bc) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - Q*HCT*C_bc + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - -(Q*HCT*C_bc) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - Q*HCT*C_bc + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - Q*(1-HCT)*C_pls + + DrugAbsorptionLumenToMucosaRate - - - + - - -(MassTransferMucosaToPvePlasmaRate) + + DrugAbsorptionLumenToMucosaRate - + - - MassTransferMucosaToPvePlasmaRate + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - + + + + + + + + + + - + + 0 + + + 0 + + Q*HCT*C_bc - - - + + + - + -(MassTransferMucosaToPveBCRate) - + - + MassTransferMucosaToPveBCRate - - - - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - - - - - - - - - + - - 0 - - - 0 - - - F1*F2*F3 + + (1-F1)*F2*F3 - - - + + + - + F1*F2*F3 - - - + + + - + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*F2*F3 - - - - + + + - - (1-F1)*F2*F3 + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - + 0 - + P_1 - + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - + + + + + + + + + + + + + - + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - + + + + + + + + + + + + + - + K_cell_pls - + - + K_water_cell - + - + -(DrugAbsorptionLumenToMucosaRate) - + - + DrugAbsorptionLumenToMucosaRate - + - + DrugAbsorptionLumenToMucosaRate - - - - - - Q*HCT*C_bc - - - - - - - - -(MassTransferMucosaToPveBCRate) - - - - - - MassTransferMucosaToPveBCRate - - - - - - -(Q*HCT*C_bc) - - - - - - - - Q*HCT*C_bc - - - - - - - - -(Q*HCT*C_bc) - - - - - - - - Q*HCT*C_bc - - - - - - - - -(Q*HCT*C_bc) - - - - - - - - Q*HCT*C_bc - - - - - - - - -(Q*HCT*C_bc) - - - - - - - - Q*HCT*C_bc - - - - - - - - 0 - - - 0 - - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - (1-F1)*F2*(1-F3) - - - - + + - - F1*(1-F2)*(1-F3) + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + + + + - - (1-F1)*(1-F2)*(1-F3) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + - - 0 - - - P_1 + + K_cell_pls - + - - F1*(1-F2)*F3 + + K_water_cell - - - + - - (1-F1)*(1-F2)*F3 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - K_water_cell + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - + + + + - - K_cell_pls + + (1-F1)*F2*F3 - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + F1*F2*F3 - - - - - - - - - - - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + (1-F1)*F2*F3 - - - - - - - - - - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + F1*(1-F2)*F3 - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + F1*F2*(1-F3) - - - - + + + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + (1-F1)*(1-F2)*F3 - - - - - - - - - - - - - - - - - F1*(1-F2)*(1-F3) + + + + + + + (1-F1)*F2*(1-F3) - - - + + + - - (1-F1)*F2*F3 + + F1*(1-F2)*(1-F3) - - - + + + - - F1*F2*F3 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*F2*F3 - - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - - (1-F1)*F2*(1-F3) + + (1-F1)*(1-F2)*F3 - - - + + + - - (1-F1)*(1-F2)*F3 + + (1-F1)*F2*(1-F3) - - - + + + - - F1*F2*(1-F3) + + F1*(1-F2)*(1-F3) - - - + + + - - F1*(1-F2)*F3 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - (1-F1)*F2*F3 + + 0 + + + P_1 - - - + - - F1*F2*F3 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - + -(DrugAbsorptionLumenToMucosaRate) - + - + DrugAbsorptionLumenToMucosaRate - + - + DrugAbsorptionLumenToMucosaRate - + - - Q*(1-HCT)*C_pls + + Q*HCT*C_bc - - - + + + - - -(MassTransferMucosaToPvePlasmaRate) + + -(MassTransferMucosaToPveBCRate) - + - - MassTransferMucosaToPvePlasmaRate + + MassTransferMucosaToPveBCRate - + - - Q*HCT*C_bc + + Q*(1-HCT)*C_pls - - - + + + - - -(MassTransferMucosaToPveBCRate) + + -(MassTransferMucosaToPvePlasmaRate) - + - - MassTransferMucosaToPveBCRate + + MassTransferMucosaToPvePlasmaRate - + - - 0 + + F1*(1-F2)*F3 + + + + + - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + F1*F2*(1-F3) - - - - - - - - - - + + + - - 0 + + (1-F1)*(1-F2)*F3 + + + + + - - Q*(1-HCT)*C_pls + + (1-F1)*F2*(1-F3) - - - + + + - - -(MassTransferMucosaToPvePlasmaRate) + + F1*(1-F2)*(1-F3) - + + + - - MassTransferMucosaToPvePlasmaRate + + (1-F1)*(1-F2)*(1-F3) - + + + - + 0 - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + P_1 - - - - - - - - - - + - - 0 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + - - F1*(1-F2)*F3 + + (1-F1)*F2*F3 - - - + + + - + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - + + + + + + + + + + + + + - + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + K_cell_pls - + - + K_water_cell - + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + F1*F2*F3 - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + (1-F1)*F2*F3 - - - - + + + - - (1-F1)*F2*F3 + + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + F1*F2*F3 - - - + + + - - (1-F1)*F2*F3 + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - F1*F2*F3 + + DrugAbsorptionLumenToMucosaRate - - - + - - (1-F1)*(1-F2)*F3 + + DrugAbsorptionLumenToMucosaRate - - - + - - F1*(1-F2)*F3 + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + - - (1-F1)*F2*(1-F3) + + 0 + + + 0 + + + Q*HCT*C_bc - - - + + + - - F1*(1-F2)*(1-F3) + + -(MassTransferMucosaToPveBCRate) - - - + - - (1-F1)*(1-F2)*(1-F3) + + MassTransferMucosaToPveBCRate + + + + + + Q*(1-HCT)*C_pls - - - + + + - - 0 - - - P_1 + + -(MassTransferMucosaToPvePlasmaRate) - + - - F1*F2*(1-F3) + + MassTransferMucosaToPvePlasmaRate - - - + - - -(DrugAbsorptionLumenToMucosaRate) + + Q*(1-HCT)*C_pls - + + + - - DrugAbsorptionLumenToMucosaRate + + -(MassTransferMucosaToPvePlasmaRate) - + - - DrugAbsorptionLumenToMucosaRate + + MassTransferMucosaToPvePlasmaRate - + - + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - + + + - - (1-F1)*F2*(1-F3) + + -(Q*HCT*C_bc) - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + Q*HCT*C_bc - - - - + + + - - (1-F1)*(1-F2)*F3 + + -(Q*HCT*C_bc) - - - + + + - - F1*F2*(1-F3) + + Q*HCT*C_bc - - - + + + - - F1*(1-F2)*F3 + + -(Q*HCT*C_bc) - - - + + + - - (1-F1)*F2*F3 + + Q*HCT*C_bc - - - + + + - - F1*F2*F3 + + -(Q*HCT*C_bc) - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + Q*HCT*C_bc - - - - + + + - - K_water_cell + + -(Q*HCT*C_bc) - + + + - - K_cell_pls + + Q*HCT*C_bc - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + -(Q*HCT*C_bc) - - - - - - - - - - - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + Q*HCT*C_bc - - - - - - - - - - - - - + + + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + -(Q*HCT*C_bc) - - - - - - - - - - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + Q*HCT*C_bc - - - - + + + - - F1*(1-F2)*(1-F3) + + -(Q*HCT*C_bc) - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + Q*HCT*C_bc - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + -(Q*HCT*C_bc) - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + Q*HCT*C_bc - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + -(Q*HCT*C_bc) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + Q*HCT*C_bc - - - - + + + - - F1*F2*F3 + + -(Q*HCT*C_bc) - - - + + + - - (1-F1)*F2*F3 + + Q*HCT*C_bc - - - + + + - - F1*(1-F2)*F3 + + -(Q*(1-HCT)*C_pls) - - - + + + - - F1*F2*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - (1-F1)*(1-F2)*F3 + + -(Q*(1-HCT)*C_pls) - - - + + + - - F1*(1-F2)*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - 0 + + -(Q*HCT*C_bc) + + + + + - - P_1 + + Q*HCT*C_bc - + + + - - (1-F1)*F2*(1-F3) + + -(Q*(1-HCT)*C_pls) - - - + + + - - -(DrugAbsorptionLumenToMucosaRate) + + Q*(1-HCT)*C_pls - + + + - - DrugAbsorptionLumenToMucosaRate + + -(IsLiverZonated ? 0 : (Q_liv +Q_pve)*HCT*C_bc) - + + + + + - - DrugAbsorptionLumenToMucosaRate + + IsLiverZonated ? 0 : (Q_liv +Q_pve)*HCT*C_bc - + + + + + - - -(IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0) + + -(IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0) - - - - - + + + + + - - IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0 + + IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0 - - - - - + + + + + - + -(IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0) - - - - - + + + + + - + IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0 - - - - - + + + + + - + -(IsLiverZonated ? 0 : (Q_liv +Q_pve)*(1-HCT)*C_pls) - - - - - + + + + + - + IsLiverZonated ? 0 : (Q_liv +Q_pve)*(1-HCT)*C_pls - - - - - + + + + + - - -(IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0) + + -(Q*HCT*C_bc) - - - - - + + + - - IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0 + + Q*HCT*C_bc - - - - - + + + - - -(IsLiverZonated ? 0 : (Q_liv +Q_pve)*HCT*C_bc) + + -(Q*(1-HCT)*C_pls) - - - - - + + + - - IsLiverZonated ? 0 : (Q_liv +Q_pve)*HCT*C_bc + + Q*(1-HCT)*C_pls - - - - - + + + - + -(IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0) - - - - - + + + + + - + IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0 - - - - - + + + + + - - -(Q*(1-HCT)*C_pls) + + -(IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0) - - - + + + + + - - Q*(1-HCT)*C_pls + + IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0 - - - + + + + + - + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - - - - - -(Q*(1-HCT)*C_pls) - - - - - - - - Q*(1-HCT)*C_pls - - - - + + + - - -(Q*HCT*C_bc) + + P_int_trans_default >0 ? P_int_trans / P_int_trans_default : 0 - - - + + - - Q*HCT*C_bc + + (f_water_rbc + f_lipids_rbc * 10^LogMA + f_proteins_rbc * KProt)*fu - - - + + + + + + - - P * P_pls_rbc_factor + + P * P_rbc_pls_factor - - + + - + 10 ^ (m * log10 (P_int_InVitro) + b) - - - + + + - + 10 ^ (m * log10 (P_int_InVitro) + b) - - - - - - - P_int_trans_default >0 ? P_int_trans / P_int_trans_default : 0 - - - + + + - - P * P_rbc_pls_factor - - - - - - - (f_water_rbc + f_lipids_rbc * 10^LogMA + f_proteins_rbc * KProt)*fu + + P * P_pls_rbc_factor - - - - - - + + - + 1 / (1 + (BindingPartner = Albumin ? AlbuminOntgenyFactor : (BindingPartner = Agp ? AgpOntogenyFactor : 1) ) * (1 - fu_ref) / fu_ref) * PlasmaProteinScaleFactor - - - - - - - + + + + + + + - + (f_water_rbc + f_lipids_rbc * 10^LogP + f_proteins_rbc * KProt) * fu * HCT - HCT + 1 - - - - - - - + + + + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Max(pKa_1;pKa_2) : (CT1 != CT_ACID ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 - - - - + + + + + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + P_1 - - - - + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Max(pKa_1;pKa_2) : (CT1 != CT_BASE ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 - - - - + + + + + + + - - F1*(1-F2)*(1-F3) + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + - - (1-F1)*F2*(1-F3) + + pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Min(pKa_1;pKa_2) : (CT1 != CT_ACID ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 - - - + + + + + + + - - (1-F1)*(1-F2)*F3 + + MW - F * 0.000000017 - Cl * 0.000000022 - Br * 0.000000062 - I * 0.000000098 - - - + + + + + - - F1*F2*(1-F3) + + pKa_Acids_Count=1 & pKa_Bases_Count = 0 ? 1 : 0 - - - + + - - F1*(1-F2)*F3 + + IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 - - - + + + - - (1-F1)*F2*F3 + + Br + Chlor + F + I > 0 - - - + + + + - - F1*F2*F3 + + pKa_Acids_Count=2 & pKa_Bases_Count = 0 ? 1 : 0 - - - + + - - (CT_0=1 AND pKa_0>=7) OR (CT_1=1 AND pKa_1>=7) OR (CT_2=1 AND pKa_2>=7) + + pKa_Acids_Count=0 & pKa_Bases_Count = 2 ? 1 : 0 - - - - - - + + - + pKa_Acids_Count=1 & pKa_Bases_Count = 2 ? 1 : 0 - - + + - - pKa_Acids_Count=1 & pKa_Bases_Count = 0 ? 1 : 0 + + pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Min(pKa_1;pKa_2) : (CT1 != CT_BASE ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 - - + + + + + + + - + pKa_Acids_Count=0 & pKa_Bases_Count = 1 ? 1 : 0 - - + + - - pKa_Acids_Count=2 & pKa_Bases_Count = 1 ? 1 : 0 + + F1*(1-F2)*F3 - - + + + - - pKa_Acids_Count=1 & pKa_Bases_Count = 1 ? 1 : 0 + + IsTriproticBase ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 - - + + + + - - pKa_TwoBases_1+pKa_ThreeBases_1 + + (CT0 = CT_BASE ? 1 : 0) + (CT1 = CT_BASE ? 1 : 0) + (CT2 = CT_BASE ? 1 : 0) - - + + + + - - CT_0 = 0 AND CT_1 = 0 AND CT_2 = 0 + + pKa_Acids_Count=1 ? (CT0=CT_ACID ? pKa_0 : (CT1=CT_ACID ? pKa_1 : pKa_2)) : 0 - - - + + + + + + + - - (CT0 = CT_ACID ? 1 : 0) + (CT1 = CT_ACID ? 1 : 0) + (CT2 = CT_ACID ? 1 : 0) + + pKa_Bases_Count=1 ? (CT0=CT_BASE ? pKa_0 : (CT1=CT_BASE ? pKa_1 : pKa_2)) : 0 - - - - + + + + + + + - - IsTriproticBase ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - pKa_Acids_Count=3 & pKa_Bases_Count = 0 ? 1 : 0 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - + + + + - - pKa_Acids_Count=0 & pKa_Bases_Count = 3 ? 1 : 0 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - + + + + - - pKa_OneAcid_0+pKa_TwoAcids_0+pKa_ThreeAcids_0 + + pKa_OneBase_0+pKa_TwoBases_0+pKa_ThreeBases_0 - - - + + + - - pKa_TwoAcids_1+pKa_ThreeAcids_1 + + (1-F1)*F2*F3 - - + + + - - IsTriproticAcid ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 + + (CT0 = CT_ACID ? 1 : 0) + (CT1 = CT_ACID ? 1 : 0) + (CT2 = CT_ACID ? 1 : 0) - - - - + + + + - - pKa_OneBase_0+pKa_TwoBases_0+pKa_ThreeBases_0 + + F1*F2*(1-F3) - - - + + + - - (CT0 = CT_BASE ? 1 : 0) + (CT1 = CT_BASE ? 1 : 0) + (CT2 = CT_BASE ? 1 : 0) + + (1-F1)*(1-F2)*F3 - - - - + + + - - pKa_Bases_Count=1 ? (CT0=CT_BASE ? pKa_0 : (CT1=CT_BASE ? pKa_1 : pKa_2)) : 0 + + (1-F1)*F2*(1-F3) - - - - - - - + + + - - pKa_Acids_Count=1 ? (CT0=CT_ACID ? pKa_0 : (CT1=CT_ACID ? pKa_1 : pKa_2)) : 0 + + F1*(1-F2)*(1-F3) - - - - - - - + + + - - IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - pKa_Acids_Count=0 & pKa_Bases_Count = 2 ? 1 : 0 + + IsTriproticAcid ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 - - + + + + - - pKa_Acids_Count=2 & pKa_Bases_Count = 0 ? 1 : 0 + + IsTriproticAcid ? (pKa_0 <= pKa_Acid_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Acid_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 - - + + + + + + - - MW - F * 0.000000017 - Cl * 0.000000022 - Br * 0.000000062 - I * 0.000000098 + + IsTriproticBase ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 - - - - - + + + + - - Br + Chlor + F + I > 0 + + IsTriproticBase ? (pKa_0 <= pKa_Base_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Base_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 - - - - + + + + + + - - (1-F1)*(1-F2)*(1-F3) + + F1*F2*F3 - - - + + + - - IsTriproticAcid ? (pKa_0 <= pKa_Acid_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Acid_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 + + pKa_Acids_Count=2 & pKa_Bases_Count = 1 ? 1 : 0 - - - - - - + + - - IsTriproticBase ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 + + pKa_Acids_Count=1 & pKa_Bases_Count = 1 ? 1 : 0 - - - - + + - - IsTriproticBase ? (pKa_0 <= pKa_Base_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Base_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 + + CT_0 = 0 AND CT_1 = 0 AND CT_2 = 0 - - - - - - + + + - - pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Min(pKa_1;pKa_2) : (CT1 != CT_ACID ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 + + (CT_0=1 AND pKa_0>=7) OR (CT_1=1 AND pKa_1>=7) OR (CT_2=1 AND pKa_2>=7) - - - - - - - + + + + + + - - pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Max(pKa_1;pKa_2) : (CT1 != CT_ACID ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 + + pKa_Acids_Count=3 & pKa_Bases_Count = 0 ? 1 : 0 - - - - - - - + + - - pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Min(pKa_1;pKa_2) : (CT1 != CT_BASE ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 + + pKa_Acids_Count=0 & pKa_Bases_Count = 3 ? 1 : 0 - - - - - - - + + - - pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Max(pKa_1;pKa_2) : (CT1 != CT_BASE ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 + + pKa_TwoBases_1+pKa_ThreeBases_1 - - - - - - - + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + pKa_OneAcid_0+pKa_TwoAcids_0+pKa_ThreeAcids_0 - - - - - - - - - - - - - - - - P_1 + + + + + + + pKa_TwoAcids_1+pKa_ThreeAcids_1 - + + - - IsTriproticAcid ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 + + IsTriproticAcid ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 - - - - + + + + - + IsSmallMolecule ? (MWEff *1E9 / 336) ^ (-6) * 10^LogMA / 5 * 1E-4 *1E-1: 0 - - - + + + - + IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 - - - + + + - + (0.81 + 0.11 * 10^LogMA) / 24.92 * 5.0 - + - + 60 * 10^(-4.113-0.4609*Log10(MW * 1E9)) *1E-2 - + - + 0,0333 * (MW * 1E9) ^ 0,4226 * 1E-8 - + - + Time=StartTime - + - + M + DrugMass - - + + - + Dose / MW - - + + - + DosePerBodyWeight * BW - - + + - + DrugMass - + - + V>0 ? M/V : 0 - - + + - + V>0 ? M/V : 0 - - + + - - 1E-09 + + 1E-10 - - 0.0001 + + 1E-05 - + 1E-10 - + 0 - + 60 - + 100000 - + 1 - + 1 - - - - - - - - - - - - + + + + + + + + + + + + - + 1 - - - - - - - - - - - - + + + + + + + + + + + + - + 1 - - - - - - - - + + - - - - - + + + + + + + + + + + - + 1 - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - + + - + 1 - + - + 1 - + - + 1 - - - - - + - + 1 - + + + + + - + 1 - + - + 1 - - - - + - + 1 - + + + + - + 1 - + - + 1 - - - - + - + 1 - + + + + - + 1 - + - + 1 - - - - + - + 1 - + + + + - + 1 - + - + 1 - - - - + - + 1 - + + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + + - + 1 - - - - - - - - - + - + 1 - - - - - - - - + + + + + + + + + - + 1 - - + + + + + + + + - + 1 - + + - + 1 - - - - - + - + 1 - - - + + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - + + - + 1 - - - + + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - + + - + 1 - - - + + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - + + - + 1 - - - + + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - + + - + 1 - - - + + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - - - - - + - + 1 - - - - - - - - - + + + + + + + + + + - + 1 - - + + + + + + + + + - + 1 - + + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - - + + - + 1 - - - - - + + + + + + - + 1 - - + + + + + - + 1 - + + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + + - + 1 - - - - + + + + + 1 + + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - - - - - - - - - - - + + + + + + + + + + + - - - + + + + + + - + 1 - - - - - - - - - - - - - + + + + + + + + + + + - - + + - + + + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - + - + 1 - + -

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- - - - - - - - + + + + + + + + diff --git a/tests/models/default man.xml b/tests/models/default man.xml index b028919..03dcba5 100644 --- a/tests/models/default man.xml +++ b/tests/models/default man.xml @@ -1,25337 +1,25688 @@ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + - + - + - - K_uptake-K_rec>=0 ? K_uptake-K_rec : 0 + + V_pls_art+V_pls_bon+V_pls_brn+V_pls_cae+V_pls_colasc+V_pls_coldesc+V_pls_colsigm+V_pls_coltrans+V_pls_duo+V_pls_fat+V_pls_tes+V_pls_hrt+V_pls_kid+V_pls_lin+V_pls_lil+V_pls_lje+V_pls_lng+V_pls_mus+V_pls_pan+V_pls_prc+V_pls_prp+V_pls_pve+V_pls_rect+V_pls_skn+V_pls_sin+V_pls_spl+V_pls_sto+V_pls_uil+V_pls_uje+V_pls_ven - - + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + - V_pls_art+V_pls_bon+V_pls_brn+V_pls_cae+V_pls_colasc+V_pls_coldesc+V_pls_colsigm+V_pls_coltrans+V_pls_duo+V_pls_fat+V_pls_tes+V_pls_hrt+V_pls_kid+V_pls_lin+V_pls_lil+V_pls_lje+V_pls_lng+V_pls_mus+V_pls_pan+V_pls_prc+V_pls_prp+V_pls_pve+V_pls_rect+V_pls_skn+V_pls_sin+V_pls_spl+V_pls_sto+V_pls_uil+V_pls_uje+V_pls_ven + K_uptake-K_rec>=0 ? K_uptake-K_rec : 0 + + + + + + + P_1 + P_2 + P_3 + P_4 + P_5 + P_6 + P_7 + P_8 + P_9 + P_10 + P_11 + P_12 + P_13 + P_14 + P_15 + P_16 + + + + + + + + + + + + + + + + + + + + + Weight_blood + Weight_tissue + + + + + + + P_1 + P_2 + P_3 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - M_art + M_sto + M_sin + M_lin + M_pan + M_spl + M_liv + M_lng + M_mus + M_fat + M_skn + M_kid + M_brn + M_hrt + M_bon + M_tes + M_pve + M_ven - - - - - - - - - - - - - - - - - - - - - - + + + + + + Age* 365.25/7 + GA - - + + - + Height>0 ? BW / (Height)^2 : 0 - - + + + + + + 1.6667 * W^0.5 * (H*10)^ 0.5 + + + - + 0.47 - + 73 - + 17.6 - + fQ_art*C_bc_art+fQ_bon*C_bc_bon+fQ_fat*C_bc_fat+fQ_mus*C_bc_mus+fQ_skn*C_bc_skn - - - - - - - - - - + + + + + + + + + + - + fQ_art*C_pls_art+fQ_bon*C_pls_bon+fQ_fat*C_pls_fat+fQ_mus*C_pls_mus+fQ_skn*C_pls_skn - - - - - - - - - - + + + + + + + + + + - + (fQ_art*C_pls_art+fQ_bon*C_pls_bon+fQ_fat*C_pls_fat+fQ_mus*C_pls_mus+fQ_skn*C_pls_skn)*fu - - - - - - - - - - - + + + + + + + + + + + - + (1-HCT)*(fQ_art*C_pls_art+fQ_bon*C_pls_bon+fQ_fat*C_pls_fat+fQ_mus*C_pls_mus+fQ_skn*C_pls_skn) + HCT*(fQ_art*C_bc_art+fQ_bon*C_bc_bon+fQ_fat*C_bc_fat+fQ_mus*C_bc_mus+fQ_skn*C_bc_skn) - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + Volume * Density - - + + - - 0.964011076649373 + + 0.964057418698908 - + Volume - + - + (1-HCT)*V - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + C_pls*fu - - + + - + Volume - + - + HCT*V - - + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + (1 - HCT) * C_pls+HCT * C_bc - - - + + + - + Volume * Density - - + + - - 0.41907815805151 + + 0.419123790014852 - + Volume - + - + (1-HCT)*V - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + C_pls*fu - - + + - + Volume - + - + HCT*V - - + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + (1 - HCT) * C_pls+HCT * C_bc - - - + + + - + 6*EHC_HalfTime - + - + V>0 ? M/V : 0 - - + + - - M/TotalDrugMass + + TotalDrugMass>0 ? M/TotalDrugMass : 0 - - + + - + Volume * Density - - + + - + Qspec * Weight - - + + - - 0.00000000000728*(BW/0.02)^0.75 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - - 0.00000068*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - + SA_pls_int*d_endo - - + + - + 1 - f_int - f_vas - - + + - + 0.027495 - - 11.8188342274097 + + 11.818939642904 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - 0.00000000000032*BW/0.02 + + SA_pls_int*d_endo - + + - - 1.55E-14*(BW/0.02)^0.75 + + f_lymph*Q*(1-HCT) - + + + - - SA_pls_int*d_endo + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 1.50917237896125 + + 1.50918505589063 - + 0.51675 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - + SA_pls_int*d_endo - - + + - - 0.00000000261*(BW/0.02)^0.75 + + f_lymph*Q*(1-HCT) - + + + - - 0.000000079*BW/0.02 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 14.6512798780623 + + 14.6541673942173 - + 0.79 - + 0.8 - + 0.002 - + 0.16 - - 0.18 - - + 0.15 - - 0.92 + + 0.18 - + 0.853 - - 0.002024 + + 0.92 - + 0.0016 - + + 0.002024 + + 0.135 - + 0.00899999999999998 - + 0.03 - + 0.02184 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - 0.00000000375*(BW/0.02)^0.75 + + SA_pls_int*d_endo - + + - - 0.000000075*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - - SA_pls_int*d_endo + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 0.040267043751193 + + 0.0402686049526551 - + 0.0806 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - SA_pls_int*d_endo + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - + + + + + + - - 0.000000198*(BW/0.02)^0.75 + + f_lymph*Q*(1-HCT) - + + + - - 0.00000081*BW/0.02 + + SA_pls_int*d_endo - + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 0.417499169226376 + + 0.417661793480006 - + 0.62335 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - + SA_pls_int*d_endo - - + + - - 0.0000000649*(BW/0.02)^0.75 + + f_lymph*Q*(1-HCT) - + + + - - 0.00000021*BW/0.02 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + 1 - f_int - f_vas - - + + - - (PMA^Hill/(TM50^Hill+PMA^Hill)*(1-GFR_premat)+GFR_premat) * GFR_mat / V_kid_std + + Age <= Age_onset ? 1 : 1 - Decrease_Factor*(Age-Age_onset)^Hill/(TA50^Hill+(Age-Age_onset)^Hill) + + + + + + + + + + GFRspec * Weight_Kidney - - - - - - + + - + + (PMA^Hill/(TM50^Hill+PMA^Hill)*(1-GFR_premat)+GFR_premat) * GFR_mat / V_kid_std * Renal_aging_scaling_factor + + + + + + + + + + + Qspec * Weight - - + + - - 0.438441657484778 + + 0.438177222622486 - - 15 + + 0.9 + + + 44.4 + + + 30 - + 0.11704 - - 44.4 + + 54 + + + 15 + + + 1.5 - + 3.02705 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + V>0 ? M/V : 0 - - + + - + V>0 ? M/V : 0 - - + + - - M/TotalDrugMass + + TotalDrugMass>0 ? M/TotalDrugMass : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + 1.00000000260982 - - Volume + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - + - - Area*d + + Liquid/V - - + + - - 1/GET + + PI*(r1+r2)*L - + + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + 1/GET - - - + - - SteadyStateFillLevel*V/StomachInflowTime + + V*SteadyStateFillLevel - - - - + + - - pH_fasted + + OralApplicationsEnabled ? -LT_sto + Inflow*FillLevelFlag : 0 - + + + + - - V*SteadyStateFillLevel + + w*Liquid*FillLevelFlagNext - - + + + - - OralApplicationsEnabled ? -LT_sto + Inflow*FillLevelFlag : 0 + + SteadyStateFillLevel*V/StomachInflowTime - - - - + + + + - - PI*(r1+r2)*L + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - + + + - - Liquid/V + + Area*d - - + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + Volume - + - - w*Liquid*FillLevelFlagNext + + pH_fasted - - - + - - 0.5 - - + 0.5 - - 1.00000002079922 + + 0.999999963215789 - + 15.0000000391473 - + + 1.00000002079922 + + 2 - - 0.999999963215789 + + 0.5 - + V>0 ? M/V : 0 - - + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + F1*F2*F3 - - - - - - - - - - - - + + + - - F1*(1-F2)*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - (1-F1)*F2*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + (1-F1)*F2*F3 - - - + + + - - F1*F2*(1-F3) + + F1*(1-F2)*F3 - - - + + + - - F1*(1-F2)*F3 + + F1*F2*(1-F3) - - - + + + - - (1-F1)*F2*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - - F1*F2*F3 + + (1-F1)*F2*(1-F3) - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + F1*(1-F2)*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + +

+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + LuminalVelocity/SITT_fact - - - + + - - r2_p0 + Height*r2_p1 + + L_p0 + Height*L_p1 - - - + + + - - Ageom*AeffFactor*AeffVariabilityFactor + + V*SteadyStateFillLevel - - - + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + OralApplicationsEnabled ? LT_sto - LT_duo + Inflow*FillLevelFlag - Outflow*Liquid : 0 - + + + + + + + - - Liquid/V + + w*Liquid*FillLevelFlagNext - - + + + - - PI*(r1+r2)*L + + r1_p0 + Height*r1_p1 - - - + + + - - LuminalVelocity/SITT_fact + + 0.02894*V - - + - - L_p0 + Height*L_p1 + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - + + + + - - V*SteadyStateFillLevel + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - + + + - - OralApplicationsEnabled ? LT_sto - LT_duo + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - - - - - + - - w*Liquid*FillLevelFlagNext + + V_Intestine * 0.087 - - - + - - r1_p0 + Height*r1_p1 + + Volume - - - + - - 0.02894*V + + PI*(r1+r2)*L - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + Liquid/V - - - - + + - - Volume + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - + + + + + + + - - V_Intestine * 0.087 + + r2_p0 + Height*r2_p1 - + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + Ageom*AeffFactor*AeffVariabilityFactor - - - - - - - + + + - + 292.6883 - + V>0 ? M/V : 0 - - + + - - (1-F1)*F2*F3 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - F1*(1-F2)*F3 + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - F1*F2*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - (1-F1)*F2*(1-F3) + + F1*F2*F3 - - - + + + - - F1*(1-F2)*(1-F3) + + (1-F1)*F2*F3 - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + F1*(1-F2)*F3 - - - + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + F1*F2*(1-F3) - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + (1-F1)*(1-F2)*F3 - - - - - - - - - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*F2*(1-F3) - - - - + + + - - F1*F2*F3 + + F1*(1-F2)*(1-F3) - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - + + + + + + + + + + + + + + + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - Ageom*AeffFactor*AeffVariabilityFactor + + LuminalVelocity/SITT_fact - - - + + - - w*Liquid*FillLevelFlagNext + + V_Intestine * 0.249 - - - + - + V*SteadyStateFillLevel - - + + - + OralApplicationsEnabled ? LT_duo - LT_uje + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - - - - - + + + + + + + - - L_p0 + Height*L_p1 + + w*Liquid*FillLevelFlagNext - - - + + + - - LuminalVelocity/SITT_fact + + r1_p0 + Height*r1_p1 - - + + + - - PI*(r1+r2)*L + + 0.0031572*V - - - + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - + + + + - - r2_p0 + Height*r2_p1 + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + Volume - - - - - - - + - - Liquid/V + + PI*(r1+r2)*L - - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + L_p0 + Height*L_p1 - - - - + + + - - r1_p0 + Height*r1_p1 + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - Volume + + r2_p0 + Height*r2_p1 - + + + - - V_Intestine * 0.249 + + Ageom*AeffFactor*AeffVariabilityFactor - + + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - 0.0031572*V + + Liquid/V - + + - + 447.9877 - + V>0 ? M/V : 0 - - + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*F3 - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*F2*(1-F3) - - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + F1*(1-F2)*F3 - - - - + + + - + (1-F1)*F2*F3 - - - - - - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - - + + + - + F1*F2*F3 - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - - - - - - - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - F1*(1-F2)*(1-F3) + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - (1-F1)*F2*(1-F3) + + F1*(1-F2)*(1-F3) - - - + + + - - (1-F1)*(1-F2)*F3 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - F1*F2*(1-F3) + + (1-F1)*F2*(1-F3) - - - + + + - - F1*(1-F2)*F3 + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + + + + +
+ + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - PI*(r1+r2)*L + + r1_p0 + Height*r1_p1 - - - + + + - - Liquid/V + + 0.0025102*V - - + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - + + + + - - Ageom*AeffFactor*AeffVariabilityFactor + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - + + + - - L_p0 + Height*L_p1 + + V_Intestine * 0.184 - - - + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + L_p0 + Height*L_p1 - - - - - - - + + + - - V*SteadyStateFillLevel + + Volume - - + - - OralApplicationsEnabled ? LT_uje - LT_lje + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + w*Liquid*FillLevelFlagNext - - - - - - - + + + - - r2_p0 + Height*r2_p1 + + V*SteadyStateFillLevel - - - + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + OralApplicationsEnabled ? LT_uje - LT_lje + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - + + + + + + + - - Volume + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - + + + + + + + - - LuminalVelocity/SITT_fact + + r2_p0 + Height*r2_p1 - - + + + - - V_Intestine * 0.184 + + Ageom*AeffFactor*AeffVariabilityFactor - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - - + - - 0.0025102*V + + Liquid/V - + + - - r1_p0 + Height*r1_p1 + + PI*(r1+r2)*L - - - + + + - - w*Liquid*FillLevelFlagNext + + LuminalVelocity/SITT_fact - - - + + - + 372.9358 - + V>0 ? M/V : 0 - - + + - - F1*F2*(1-F3) + + F1*(1-F2)*(1-F3) - - - + + + - - (1-F1)*F2*(1-F3) + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - F1*(1-F2)*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + F1*F2*F3 - - - - - - - - - - - - - - - - F1*(1-F2)*F3 + + + + + + + (1-F1)*F2*F3 - - - + + + - - (1-F1)*(1-F2)*F3 + + F1*(1-F2)*F3 - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + F1*F2*(1-F3) - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + (1-F1)*F2*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - F1*F2*F3 + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + - - (1-F1)*F2*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - LuminalVelocity/SITT_fact + + r2_p0 + Height*r2_p1 - - + + + - - L_p0 + Height*L_p1 + + r1_p0 + Height*r1_p1 - - - + + + - - V*SteadyStateFillLevel + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - + + + + + + + - - OralApplicationsEnabled ? LT_lje - LT_uil + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + Ageom*AeffFactor*AeffVariabilityFactor - - - - - - - + + + - - w*Liquid*FillLevelFlagNext + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - r1_p0 + Height*r1_p1 + + Liquid/V - - - + + - - 0.0029585*V + + PI*(r1+r2)*L - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + LuminalVelocity/SITT_fact - - - - + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + L_p0 + Height*L_p1 - - - + + + - - V_Intestine * 0.324 + + V*SteadyStateFillLevel - + + - - Volume + + OralApplicationsEnabled ? LT_lje - LT_uil + Inflow*FillLevelFlag - Outflow*Liquid : 0 - + + + + + + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + 0.0029585*V - + - - PI*(r1+r2)*L + + w*Liquid*FillLevelFlagNext - - - + + + - - Ageom*AeffFactor*AeffVariabilityFactor + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - + + + + - - r2_p0 + Height*r2_p1 + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + V_Intestine * 0.324 - - - - - - - + - - Liquid/V + + Volume - - + - + 260.7527 - + V>0 ? M/V : 0 - - + + - - F1*F2*(1-F3) + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + + + + +
+ + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + (1-F1)*(1-F2)*(1-F3) - - - - - - - - - - - - + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + F1*(1-F2)*(1-F3) - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + (1-F1)*F2*(1-F3) - - - + + + - - F1*(1-F2)*(1-F3) + + (1-F1)*(1-F2)*F3 - - - + + + - - (1-F1)*(1-F2)*F3 + + F1*F2*(1-F3) - - - + + + - + F1*(1-F2)*F3 - - - + + + - + (1-F1)*F2*F3 - - - + + + - + F1*F2*F3 - - - + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - - + + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - - - - - - - (1-F1)*F2*(1-F3) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - V_Intestine * 0.156 + + PI*(r1*r1+r1*r2+r2*r2)/3*L - + + + - - Volume + + V_Intestine * 0.156 - + - - Ageom*AeffFactor*AeffVariabilityFactor + + Volume - - - + - - V*SteadyStateFillLevel + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - + + + + - - OralApplicationsEnabled ? LT_uil - LT_lil + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - - - - - + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + Ageom*AeffFactor*AeffVariabilityFactor - - - - + + + - - 0.0017657*V + + Liquid/V - + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + PI*(r1+r2)*L - - - - - - - + + + - - w*Liquid*FillLevelFlagNext + + LuminalVelocity/SITT_fact - - - + + - - r2_p0 + Height*r2_p1 + + L_p0 + Height*L_p1 - - - + + + - - L_p0 + Height*L_p1 + + V*SteadyStateFillLevel - - - + + - - LuminalVelocity/SITT_fact + + OralApplicationsEnabled ? LT_uil - LT_lil + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - + + + + + + + - - PI*(r1+r2)*L + + w*Liquid*FillLevelFlagNext - - - + + + - - Liquid/V + + r1_p0 + Height*r1_p1 - - + + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + 0.0017657*V - + - - r1_p0 + Height*r1_p1 + + r2_p0 + Height*r2_p1 - - - + + + - + 146.565 - + V>0 ? M/V : 0 - - + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + +
+ + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - + + + + + + + + + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + F1*F2*F3 - - - + + + - + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - - (1-F1)*(1-F2)*(1-F3) - - - - - - - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + F1*(1-F2)*(1-F3) - - - - - - - - - - - - + + + - - F1*(1-F2)*(1-F3) + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + Volume - - - + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + V_Intestine * 0.08470588 - - - - - - - + - - r2_p0 + Height*r2_p1 + + LuminalVelocity/LITT_fact - - - + + - - Ageom*AeffFactor*AeffVariabilityFactor + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + r2_p0 + Height*r2_p1 - + + + - - Liquid/V + + Ageom*AeffFactor*AeffVariabilityFactor - - + + + - - PI*(r1+r2)*L + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - LuminalVelocity/LITT_fact + + PI*(r1+r2)*L - - + + + - + L_p0 + Height*L_p1 - - - + + + - + V*SteadyStateFillLevel - - + + - + OralApplicationsEnabled ? LT_lil - LT_cae + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - - - - - + + + + + + + - + w*Liquid*FillLevelFlagNext - - - + + + - + r1_p0 + Height*r1_p1 - - - + + + - + 0*V - + - + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - - + + + + - - Volume + + Liquid/V - + + - - V_Intestine * 0.08470588 + + PI*(r1*r1+r1*r2+r2*r2)/3*L - + + + - + 1.8 - + V>0 ? M/V : 0 - - + + - - F1*F2*F3 + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + + F1*F2*F3 + + + + + + + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - - F1*(1-F2)*(1-F3) - - - - - - - + (1-F1)*(1-F2)*(1-F3) - - - - - - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor - - - - + + + - + +
+ + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - - - - - - - - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + + + + + + + + F1*(1-F2)*(1-F3) - - - - + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + Volume - - - - + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + V_Intestine * 0.15529412 - - - + - - V_Intestine * 0.15529412 + + V*SteadyStateFillLevel - + + - - Volume + + OralApplicationsEnabled ? LT_cae - LT_colasc + Inflow*FillLevelFlag - Outflow*Liquid : 0 - + + + + + + + - - r1_p0 + Height*r1_p1 + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - w*Liquid*FillLevelFlagNext + + r2_p0 + Height*r2_p1 - - - + + + - - 0.00098426*V + + Ageom*AeffFactor*AeffVariabilityFactor - + + + - - r2_p0 + Height*r2_p1 + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - V*SteadyStateFillLevel + + Liquid/V - - + + - - OralApplicationsEnabled ? LT_cae - LT_colasc + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + PI*(r1+r2)*L - - - - - - - + + + - + L_p0 + Height*L_p1 - - - + + + - - LuminalVelocity/LITT_fact + + w*Liquid*FillLevelFlagNext - - + + + - - PI*(r1+r2)*L + + r1_p0 + Height*r1_p1 - - - + + + - - Liquid/V + + 0.00098426*V - - + - - Ageom*AeffFactor*AeffVariabilityFactor + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - + + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - - - - - + + + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + LuminalVelocity/LITT_fact - + + - + 2.5 - + V>0 ? M/V : 0 - - + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + (1-F1)*F2*(1-F3) - - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + F1*(1-F2)*(1-F3) - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - + + + + + + + + + + + + + + + + F1*F2*(1-F3) + + + + - - F1*F2*F3 + + F1*(1-F2)*F3 - - - + + + - - (1-F1)*F2*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - - F1*(1-F2)*F3 + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - F1*F2*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - F1*(1-F2)*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + F1*F2*F3 - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - - - - - - - - - - (1-F1)*F2*(1-F3) + + (1-F1)*F2*F3 - - - + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - V*SteadyStateFillLevel + + r1_p0 + Height*r1_p1 - - + + + - - OralApplicationsEnabled ? LT_colasc - LT_coltrans + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + r2_p0 + Height*r2_p1 - - - - - - - + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + Ageom*AeffFactor*AeffVariabilityFactor - - - - - - - + + + - - r2_p0 + Height*r2_p1 + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + Liquid/V - + + - + PI*(r1+r2)*L - - - + + + - - Volume + + LuminalVelocity/LITT_fact - + + - - V_Intestine * 0.32 + + L_p0 + Height*L_p1 - + + + - - LuminalVelocity/LITT_fact + + w*Liquid*FillLevelFlagNext - - + + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + 0.00020285*V - - - + - - L_p0 + Height*L_p1 + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - + + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - - + + + - - 0.00020285*V + + V_Intestine * 0.32 - + - - r1_p0 + Height*r1_p1 + + Volume - - - + - - w*Liquid*FillLevelFlagNext + + V*SteadyStateFillLevel - - - + + - - Ageom*AeffFactor*AeffVariabilityFactor + + OralApplicationsEnabled ? LT_colasc - LT_coltrans + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - + + + + + + + - - Liquid/V + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - + + + + + + + - + 2.5 - + V>0 ? M/V : 0 - - + + - - (1-F1)*F2*(1-F3) + + (1-F1)*(1-F2)*F3 - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + (1-F1)*F2*(1-F3) - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*(1-F2)*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - F1*F2*F3 + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + - + (1-F1)*F2*F3 - - - + + + - - F1*(1-F2)*F3 + + F1*F2*(1-F3) - - - + + + - - (1-F1)*(1-F2)*F3 + + F1*(1-F2)*F3 - - - + + + - - F1*(1-F2)*(1-F3) + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - - - - - - - - - - - - - F1*F2*(1-F3) + + + + + + + + F1*F2*F3 - - - + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - + Ageom*AeffFactor*AeffVariabilityFactor - - - + + + - - r2_p0 + Height*r2_p1 + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - - - - - + + + + - - PI*(r1+r2)*L + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - - - + - - (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + Liquid/V - + + - - 0.00023004*V + + PI*(r1+r2)*L - + + + - - V_Intestine * 0.24 + + LuminalVelocity/LITT_fact - + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + L_p0 + Height*L_p1 - - - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + V*SteadyStateFillLevel - - - - + + - - r1_p0 + Height*r1_p1 + + OralApplicationsEnabled ? LT_coltrans - LT_coldesc + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - + + + + + + + - + w*Liquid*FillLevelFlagNext - - - + + + - - V*SteadyStateFillLevel + + 0.00023004*V - - + - - OralApplicationsEnabled ? LT_coltrans - LT_coldesc + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + PI*(r1*r1+r1*r2+r2*r2)/3*L - - - - - - - + + + - - L_p0 + Height*L_p1 + + V_Intestine * 0.24 - - - + - - LuminalVelocity/LITT_fact + + Volume - - + - - Liquid/V + + r2_p0 + Height*r2_p1 - - + + + - - Volume + + r1_p0 + Height*r1_p1 - + + + - + 2.5 - + V>0 ? M/V : 0 - - + + - - (1-F1)*(1-F2)*F3 + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + - - (1-F1)*F2*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - F1*(1-F2)*(1-F3) + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + F1*F2*F3 - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + (1-F1)*F2*F3 - - - - - - - - - - - - - - - + + + + + + F1*(1-F2)*F3 - - - + + + - - (1-F1)*F2*F3 + + F1*F2*(1-F3) - - - + + + - - F1*F2*(1-F3) + + (1-F1)*(1-F2)*F3 - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + (1-F1)*F2*(1-F3) - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*(1-F2)*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - - + + + + - - F1*F2*F3 + +
+ + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - - Volume + + PI*(r1*r1+r1*r2+r2*r2)/3*L - + + + - - V_Intestine * 0.135 + + PI*(r1+r2)*L - + + + - - (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + LuminalVelocity/LITT_fact - - - - - - - + + - - r2_p0 + Height*r2_p1 + + L_p0 + Height*L_p1 - - - + + + - + V*SteadyStateFillLevel - - + + - + OralApplicationsEnabled ? LT_coldesc - LT_colsigm + Inflow*FillLevelFlag - Outflow*Liquid : 0 - - - - - - - + + + + + + + - - PI*(r1*r1+r1*r2+r2*r2)/3*L + + w*Liquid*FillLevelFlagNext - - - + + + - - Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + r1_p0 + Height*r1_p1 - - - - + + + - + 0.00013099*V - + - - w*Liquid*FillLevelFlagNext + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - + + + + - - L_p0 + Height*L_p1 + + Ageom*AeffFactor*AeffVariabilityFactor - - - + + + - - LuminalVelocity/LITT_fact + + V_Intestine * 0.135 - - + - - PI*(r1+r2)*L + + Volume - - - + - + Liquid/V - - + + - + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - + - - Ageom*AeffFactor*AeffVariabilityFactor + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - + + + + + + + - - r1_p0 + Height*r1_p1 + + r2_p0 + Height*r2_p1 - - - + + + - + 2.5 - + V>0 ? M/V : 0 - - + + - + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + F1*F2*F3 - - - + + + - + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - - - - - F1*(1-F2)*(1-F3) - - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + + + + + + + + + + + + + + + F1*(1-F2)*(1-F3) - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - - - - - - - - - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - - - - - PI*(r1*r1+r1*r2+r2*r2)/3*L - - - - + + - + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) - - - - - - - + + + + + + + - + r2_p0 + Height*r2_p1 - - - + + + - + Ageom*AeffFactor*AeffVariabilityFactor - - - + + + - + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) - + - + Liquid/V - - + + - - PI*(r1+r2)*L + + L_p0 + Height*L_p1 - - - + + + - - LuminalVelocity/LITT_fact + + PI*(r1+r2)*L - - + + + - - L_p0 + Height*L_p1 + + V_Intestine * 0.055 - - - + - + V*SteadyStateFillLevel - - + + - + OralApplicationsEnabled ? LT_colsigm - LT_rect + Inflow*FillLevelFlag : 0 - - - - - + + + + + - + w*Liquid - - + + - + r1_p0 + Height*r1_p1 - - - + + + - + 0.00071247*V - + - + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) - - - - + + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + - + Volume - + - - V_Intestine * 0.055 + + LuminalVelocity/LITT_fact - + + - + 3.56 - + V>0 ? M/V : 0 - - + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - - - - - - - - - - PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + F1*(1-F2)*(1-F3) - - - - + + + - - Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) - - - + + + + - - (1-F1)*(1-F2)*(1-F3) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - F1*(1-F2)*(1-F3) + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable - - - + + + + - - (1-F1)*F2*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + F1*F2*F3 - - - + + + - - F1*F2*(1-F3) + + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - - (1-F1)*F2*F3 + + F1*F2*(1-F3) - - - + + + - - F1*F2*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + (1-F1)*F2*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + min(Solubility/MW ; M/Liquid) - - - - + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - + OralApplicationsEnabled ? LT_rec : 0 - - + + - + V>0 ? M/V : 0 - - + + - - M/TotalDrugMass + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 - - + + - + TotalOralDrugMass > 0 ? (M_sto + M_duo + M_uje + M_lje + M_uil + M_lil + M_cae + M_colasc + M_coltrans + M_coldesc + M_colsigm + M_rect + M_fec + Mabs_Mucosa) / TotalOralDrugMass : 0 - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + - + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 - - + + - + Volume * Density - - + + - - 0.000000066*BW/0.02 + + SA_pls_int*d_endo - + + - - SA_pls_int*d_endo + + f_lymph*Q*(1-HCT) - - + + + - - 0.00000000543*(BW/0.02)^0.75 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 0.168499219491006 + + 0.168512927754721 - + 0.3861 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - + P1*SITT+P2 - - - + + + - - SA_pls_int*d_endo + + J_iso_incl_Mucosa-J_iso_duo-J_iso_uje-J_iso_lje-J_iso_uil-J_iso_lil - - + + + + + + - - 0.00000012*BW/0.02 + + SA_pls_int*d_endo - + + - - Q_lymph_incl_Mucosa-Q_lymph_duo-Q_lymph_uje-Q_lymph_lje-Q_lymph_uil-Q_lymph_lil + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - - - - - + + + + + + - - 0.00000000421*(BW/0.02)^0.75 + + Q_lymph_incl_Mucosa-Q_lymph_duo-Q_lymph_uje-Q_lymph_lje-Q_lymph_uil-Q_lymph_lil - + + + + + + - - J_iso_incl_Mucosa-J_iso_duo-J_iso_uje-J_iso_lje-J_iso_uil-J_iso_lil + + f_lymph*Q*(1-HCT) - - - - - - + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - + V_duo+V_uje+V_lje+V_uil+V_lil - - - - - + + + + + - + 126.000000328837 - - 0.724535824704532 + + 0.724543779958711 - + 0.89765 - + Volume - + - + f_vas*(1-HCT)*(V-V_Mucosa) - - - - + + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*(V-V_Mucosa) - - - - + + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*(V-V_Mucosa) - - - + + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume-V_Mucosa - - + + - + f_cell*(V-V_Mucosa) - - - + + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - Q_lymph_intestine * V_seg / V_intestine + + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - Q_lymph_intestine * V_seg / V_intestine + + J_iso_intestine * V_seg / V_intestine - - - + + + - + SA_pls_int*d_endo - - + + - - J_iso_intestine * V_seg / V_intestine + + Q_lymph_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - Q_lymph_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + J_iso_intestine * V_seg / V_intestine - - + + + - + Q_lymph_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - - Q_lymph_intestine * V_seg / V_intestine + + J_iso_intestine * V_seg / V_intestine - - - + + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (M_int + M_cell + M_int_duo + M_cell_duo + M_int_uje + M_cell_uje + M_int_lje + M_cell_lje + M_int_uil + M_cell_uil + M_int_lil + M_cell_lil)/(V_int + V_cell + V_int_duo + V_cell_duo + V_int_uje + V_cell_uje + V_int_lje + V_cell_lje + V_int_uil + V_cell_uil + V_int_lil + V_cell_lil) - - - - - - - - - - - - - - - - - - - - - - - - - - - - P1*LITT+P2 + + + + + + + + + + + + + + + + + + + + + + + + + + + + Volume * Density - - - + + - + V_cae+V_ca+V_ct+V_cd+V_cs+V_rec - - - - - - + + + + + + - - Volume * Density + + P1*LITT+P2 - - + + + - - J_iso_incl_Mucosa-J_iso_cae-J_iso_colasc-J_iso_coltrans-J_iso_coldesc-J_iso_colsigm-J_iso_rect + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - - - - - - + + + + + + - - 0.000000000705*(BW/0.02)^0.75 + + SA_pls_int*d_endo - + + - + Q_lymph_incl_Mucosa-Q_lymph_cae-Q_lymph_colasc-Q_lymph_coltrans-Q_lymph_coldesc-Q_lymph_colsigm-Q_lymph_rect - - - - - - - + + + + + + + - - 0.00000034*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - - SA_pls_int*d_endo + + J_iso_incl_Mucosa-J_iso_cae-J_iso_colasc-J_iso_coltrans-J_iso_coldesc-J_iso_colsigm-J_iso_rect - - + + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - + 2652 - - 0.412507067198975 + + 0.412534533496838 - + 0.6305 - + Volume - + - + f_vas*(1-HCT)*(V-V_Mucosa) - - - - + + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*(V-V_Mucosa) - - - - + + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*(V-V_Mucosa) - - - + + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume-V_Mucosa - - + + - + f_cell*(V-V_Mucosa) - - - + + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - Q_lymph_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - - Q_lymph_intestine * V_seg / V_intestine + + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - Q_lymph_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - Q_lymph_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + J_iso_intestine * V_seg / V_intestine - - + + + - - J_iso_intestine * V_seg / V_intestine + + Q_lymph_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - - SA_pls_int*d_endo + + Q_lymph_intestine * V_seg / V_intestine - - + + + - - Q_lymph_intestine * V_seg / V_intestine + + J_iso_intestine * V_seg / V_intestine - - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + Volume * Density - - + + - + V_GutWall*fractionMucosa - - + + - - J_iso_intestine * V_seg / V_intestine + + SA_pls_int*d_endo - - - + + - + Q_lymph_intestine * V_seg / V_intestine - - - + + + - - SA_pls_int*d_endo + + J_iso_intestine * V_seg / V_intestine - - + + + - + Q * fractQ * regionalFractQ - - - + + + - + 1 - f_int - f_vas - - + + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (M_int + M_cell + M_int_cae + M_cell_cae + M_int_colasc + M_cell_colasc + M_int_coltrans + M_cell_coltrans + M_int_coldesc + M_cell_coldesc + M_int_colsigm + M_cell_colsigm + M_int_rect + M_cell_rect)/(V_int + V_cell + V_int_cae + V_cell_cae + V_int_colasc + V_cell_colasc + V_int_coltrans + V_cell_coltrans + V_int_coldesc + V_cell_coldesc + V_int_colsigm + V_cell_colsigm + V_int_rect + V_cell_rect) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + Volume * Density - - + + - - SA_pls_int*d_endo + + f_lymph*Q*(1-HCT) - - + + + - - 0.0000091*BW/0.02 + + SA_pls_int*d_endo - + + - - 0.00000169*(BW/0.02)^0.75 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 2.37706249474073 + + 2.37687829215356 - + 0.1794 - - Volume * Density + + Liver_Parameter - - + - + Liver_Parameter - + - + Liver_Parameter - + - - Liver_Parameter + + Volume * Density - + + - + V_liv * (IsLiverZonated ? f_periportal : 1) - - - + + + - + Liver_Parameter - + - - J_iso * (IsLiverZonated? f_periportal : 1) + + Liver_Parameter - - - + - - Liver_Parameter + + SA_pls_int*d_endo - + + - - SA_pls_int*d_endo + + Q_lymph * (IsLiverZonated? f_periportal : 1) - - + + + - + Liver_Parameter - + - - Q_lymph * (IsLiverZonated? f_periportal : 1) + + J_iso * (IsLiverZonated? f_periportal : 1) - - - + + + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + pH_cell_Liver - + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Volume * Density - - + + - + V_liv * (IsLiverZonated ? 1 - f_periportal : 0) - - - + + + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - - SA_pls_int*d_endo + + Q_lymph * (IsLiverZonated? 1-f_periportal : 0) - - + + + - + J_iso * (IsLiverZonated? 1-f_periportal : 0) - - - + + + - - Q_lymph * (IsLiverZonated? 1-f_periportal : 0) + + SA_pls_int*d_endo - - - + + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Liver_Parameter - + - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + pH_cell_Liver - + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + f_vas*(1-HCT)*V_org - - - + + + - + (C_pls_prp * V_pls_prp + C_pls_prc * V_pls_prc)/(V_pls_prp+V_pls_prc) - - - - + + + + - + f_vas*HCT*V - - - + + + - + (C_bc_prp * V_bc_prp + C_bc_prc * V_bc_prc)/(V_bc_prp+V_bc_prc) - - - - + + + + - + f_int*V - - + + - + pH_int - + - + (C_int_prp * V_int_prp + C_int_prc * V_int_prc)/(V_int_prp+V_int_prc) - - - - + + + + - + f_cell*V - - + + - + (C_cell_prp * V_cell_prp + C_cell_prc * V_cell_prc)/(V_cell_prp+V_cell_prc) - - - - + + + + - + (C_int_prp * K_water_int_prp * V_int_prp + C_int_prc * K_water_int_prc * V_int_prc)/(V_int_prp+V_int_prc) - - - - - - + + + + + + - + (C_cell_prp * K_water_cell_prp * V_cell_prp + C_cell_prc * K_water_cell_prc * V_cell_prc)/(V_cell_prp+V_cell_prc) - - - - - - + + + + + + - + (C_int_prp * V_int_prp + C_int_prc * V_int_prc + C_cell_prp * V_cell_prp + C_cell_prc * V_cell_prc)/(V_int_prp+V_int_prc+V_cell_prp) - - - - - - - - + + + + + + + + - + Volume * Density - - + + - - 0.000000000301*(BW/0.02)^0.75 + + f_lymph*Q*(1-HCT) - + + + - - 0.000005*BW/0.02 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + SA_pls_int*d_endo - - + + - + 1 - f_int - f_vas - - + + - + Q_sto + Q_sin + Q_lin + Q_pan + Q_spl + Q_liv + Q_mus + Q_fat + Q_skn + Q_kid + Q_brn + Q_hrt + Q_bon + Q_tes - - - - - - - - - - - - - - - - - - 1.21437445957892 - - + + + + + + + + + + + + + + + + + + 1.21442334117614 + + 0.58 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - SA_pls_int*d_endo + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - + + + + + + - - 0.000000111*(BW/0.02)^0.75 + + SA_pls_int*d_endo - + + - - 0.00000055*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 32.6464810527863 - - - 0.013 + + 32.6437428514658 - + 0.0238 - + + 0.013 + + 0.177 - + 0.0072 - + 0.76 - + 0.811 - + 0.16 - + 0.0049 - + 0.022 - + 0.0042 - + 0.0078 - + 0.079 - + 0.19 - + 0.666 - + 0.76 - + 0.03419 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - 0.0000000872*(BW/0.02)^0.75 + + SA_pls_int*d_endo - + + - - SA_pls_int*d_endo + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - - + + + + + + - - 0.00000065*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 0.19040446555646 + + 0.190400933675117 - + 0.3419 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - + Q_Lymph_sto + Q_Lymph_sin_incl_Mucosa + Q_Lymph_lin_incl_Mucosa + Q_Lymph_pan + Q_Lymph_spl - - - - - + + + + + - + Q_sto + Q_sin + Q_lin + Q_pan + Q_spl - - - - - + + + + + - - 1.03740287497562 + + 1.03739587237417 - + Volume - + - + (1-HCT)*V - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + C_pls*fu - - + + - + Volume - + - + HCT*V - - + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + (1 - HCT) * C_pls+HCT * C_bc - - - + + + - + Volume * Density - - + + - - 0.000000342*(BW/0.02)^0.75 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - + SA_pls_int*d_endo - - + + - - 0.00000051*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - - + + - - 3.76314310880436 + + 3.76303501298772 - + 0.08645 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - - 0.0000000000961*(BW/0.02)^0.75 + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) - + + + + + + - - 0.000008*BW/0.02 + + f_lymph*Q*(1-HCT) - + + + - + SA_pls_int*d_endo - - + + - + 1 - f_int - f_vas - - + + - + Qspec * Weight - + - - 0.207006158806892 + + 0.206951734466372 - + 0.801125 - + Volume - + - + f_vas*(1-HCT)*V_org - - - + + + - + V>0 ? M/V : 0 - - + + - + fu - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_vas*HCT*V - - - + + + - + V>0 ? M/V : 0 - - + + - + K_rbc/fu - - + + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_int*V - - + + - + pH_int - + - + V>0 ? M/V : 0 - - + + - + K_water_int - + - + V>0 ? M/V : 0 - - + + - + Volume - + - + f_cell*V - - + + - + V>0 ? M/V : 0 - - + + - + K_water_cell - + - + V>0 ? M/V : 0 - - + + - + C_int * K_water_int - - + + - + C_cell * K_water_cell - - + + - + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) - - - - + + + + - + Volume * Density - - + + - + 0.006 * BW / 73 - + - + V_slv - + - + V>0 ? M/V : 0 - - + + - + V>0 ? M/V : 0 - - + + - + V_slv - + - + V>0 ? M/V : 0 - - + + - + V>0 ? M/V : 0 - - + + - - -(Q*HCT*C_bc) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - + + + + + + + - - Q*HCT*C_bc + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - + + + + + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + HCT * A_to_V_bc * 0.6 * V - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(Q*(1-HCT)*C_pls) - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * V + + Q*(1-HCT)*C_pls - - - + + + - - -(Q*(1-HCT)*C_pls) + + -(Q*HCT*C_bc) - - - + + + - - Q*(1-HCT)*C_pls + + Q*HCT*C_bc - - - + + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V - - - + + + - + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - + + + - - P_int_cell * SA + + P_cell_int * SA - - + + - - P * P_cell_int_factor + + fu/K_cell_pls - - + + - - P_cell_int * SA - - - + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + + + + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P_int_cell * SA - - - - - - + + - - fu/K_cell_pls + + P * P_cell_int_factor - - + + - + P * P_int_cell_factor - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_bon * 1000 / 28.2)^0.75 * 10 * 1E2 - + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - + -(Q*(1-HCT)*C_pls) - - - + + + - + Q*(1-HCT)*C_pls - - - - - - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - - + + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + P_cell_int * SA - - - - + + - - P/2 + + P_int_cell * SA - + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + P * P_cell_int_factor - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + P * P_int_cell_factor - - - - - - + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + fu/K_cell_pls - - - - - - + + - - k * f_vas_org * V_org + + fu/K_int_pls - - - + + - - -(Q*HCT*C_bc) + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - + + + + + + - - Q*HCT*C_bc + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - + + + + + + - - fu/K_cell_pls + + (V_brn * 1000 / 1.671)^0.75 * 0.0006 * 1E2 - - + - - P * P_int_cell_factor + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - + + + + + + + - - P * P_cell_int_factor + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - + + + + + + + - - P_int_cell * SA + + HCT * A_to_V_bc * 0.6 * V * f_vas - - + + + + - - P_cell_int * SA + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - + + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P/2 - - - - - - + - - fu/K_int_pls + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - + + + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + k * f_vas_org * V_org - - - - - - + + + - - (V_brn * 1000 / 1.671)^0.75 * 0.0006 * 1E2 + + -(Q*(1-HCT)*C_pls) - + + + - - -(Q*(1-HCT)*C_pls) + + Q*(1-HCT)*C_pls - - - + + + - - Q*(1-HCT)*C_pls + + -(Q*HCT*C_bc) - - - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + Q*HCT*C_bc - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(Q*(1-HCT)*C_pls) - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + Q*(1-HCT)*C_pls - - - - + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - -(Q*(1-HCT)*C_pls) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - + + + + + + + - - Q*(1-HCT)*C_pls + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - + + + + + + + - - P * P_int_cell_factor + + HCT * A_to_V_bc * 0.6 * V * f_vas - - + + + + - - P_int_cell * SA + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - - P_cell_int * SA + + fu/K_cell_pls - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P_cell_int * SA - - - - - - + + - - fu/K_cell_pls + + P_int_cell * SA - - + + - + P * P_cell_int_factor - - + + - + + P * P_int_cell_factor + + + + + + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_fat * 1000 / 14.2)^0.75 * 5 * 1E2 - + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + -(Q*HCT*C_bc) - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + Q*HCT*C_bc - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + -(Q*(1-HCT)*C_pls) - - - - + + + - - -(Q*HCT*C_bc) + + Q*(1-HCT)*C_pls - - - + + + - - Q*HCT*C_bc + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - + + + + - - fu/K_cell_pls + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - + + + + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - - P * P_int_cell_factor + + k * f_vas_org * V_org - - + + + - - P * P_cell_int_factor + + fu/K_cell_pls - - + + - - P_int_cell * SA + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - + P_cell_int * SA - - + + - - fu/K_int_pls + + P_int_cell * SA - - + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + P * P_cell_int_factor - - - - - - + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + P * P_int_cell_factor - - - - - - + + - - (V_tes * 1000 / 2.5)^0.75 * 2 * 1E2 + + fu/K_int_pls - + + - - -(Q*(1-HCT)*C_pls) + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - + + + + + + - - Q*(1-HCT)*C_pls + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - + + + + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + (V_tes * 1000 / 2.5)^0.75 * 2 * 1E2 - - - - + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - + + + + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - + + + + + + + - - k * f_vas_org * V_org + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - + + + + - + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - + + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + P_cell_int * SA - - - - - - - + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - - + + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + fu/K_cell_pls - - - - + + - - -(Q*(1-HCT)*C_pls) + + P * P_int_cell_factor - - - + + - - Q*(1-HCT)*C_pls + + P * P_cell_int_factor - - - + + - - -(Q*HCT*C_bc) + + P_int_cell * SA - - - + + - - Q*HCT*C_bc + + fu/K_int_pls - - - + + - - P * P_int_cell_factor + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - + + + + + + - - P * P_cell_int_factor + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - + + + + + + - - P_int_cell * SA + + (V_hrt * 1000 / 1.2)^0.75 * 7.54 * 1E2 - - + - - P_cell_int * SA + + -(Q*HCT*C_bc) - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + Q*HCT*C_bc - - - - - - + + + - - fu/K_cell_pls + + -(fu * TSspec * V_kid * C_kid_pls * Renal_aging_scaling_factor) - - + + + + + - - fu/K_int_pls + + fu * TSspec * V_kid * C_kid_pls * Renal_aging_scaling_factor - - + + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + TS / V_kid - - - - - - + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + -(fu * GFRspec*GFR_Fraction* Weight_Kidney * C_kid_pls) - - - - - - + + + + + - - (V_hrt * 1000 / 1.2)^0.75 * 7.54 * 1E2 + + fu * GFRspec*GFR_Fraction* Weight_Kidney * C_kid_pls - + + + + + - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + Q*HCT*C_bc - - - - - - - - - - + + + - - 0 - - - P_1 + + -(MassTransferMucosaToPveBCRate) - + - - -(DrugAbsorptionLumenToMucosaRate) + + MassTransferMucosaToPveBCRate - + - - DrugAbsorptionLumenToMucosaRate + + Q*(1-HCT)*C_pls - + + + - - DrugAbsorptionLumenToMucosaRate + + -(MassTransferMucosaToPvePlasmaRate) - + - - F1*F2*(1-F3) + + MassTransferMucosaToPvePlasmaRate - - - + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - - - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - - - K_cell_pls - - - + + 0 - - K_water_cell + + (1-F1)*(1-F2)*(1-F3) - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + P_1 - - - - + - + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + F1*F2*F3 - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*F2*F3 - - - - + + + - - (1-F1)*F2*(1-F3) + + F1*(1-F2)*F3 - - - + + + - + + F1*F2*(1-F3) + + + + + + + (1-F1)*(1-F2)*F3 - - - + + + - - F1*F2*(1-F3) + + (1-F1)*F2*(1-F3) - - - + + + - - F1*(1-F2)*F3 + + F1*(1-F2)*(1-F3) - - - + + + - - (1-F1)*F2*F3 + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - (1-F1)*F2*F3 + + K_water_cell - - - + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - - F1*(1-F2)*F3 + + F1*F2*F3 - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + (1-F1)*F2*F3 - - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + F1*(1-F2)*F3 - - - + + + - - F1*(1-F2)*(1-F3) + + F1*F2*(1-F3) - - - + + + - + + (1-F1)*(1-F2)*F3 + + + + + + + (1-F1)*F2*(1-F3) - - - + + + - - (1-F1)*(1-F2)*F3 + + F1*(1-F2)*(1-F3) - - - + + + - - F1*F2*F3 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - 0 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + - - F1*(1-F2)*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - P_1 + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - + + + + + + + + + + + + + - - (1-F1)*(1-F2)*(1-F3) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + - - -(DrugAbsorptionLumenToMucosaRate) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - + + + + + + + + + + + + + + + + + K_cell_pls + + - - DrugAbsorptionLumenToMucosaRate + + -(DrugAbsorptionLumenToMucosaRate) - + - + DrugAbsorptionLumenToMucosaRate - + - - Q*(1-HCT)*C_pls + + DrugAbsorptionLumenToMucosaRate - - - + - - -(MassTransferMucosaToPvePlasmaRate) + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - + + + + + + + + + + - - MassTransferMucosaToPvePlasmaRate + + 0 + + + P_1 - + - - P * P_int_cell_factor + + -(DrugAbsorptionLumenToMucosaRate) - - + - - P * P_cell_int_factor + + DrugAbsorptionLumenToMucosaRate - - + - - P_int_cell * SA + + DrugAbsorptionLumenToMucosaRate - - + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + -(Q*(1-HCT)*C_pls) - - - - - - + + + - - fu/K_cell_pls + + Q*(1-HCT)*C_pls - - + + + - - P_cell_int * SA + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - + + + + - - fu/K_int_pls + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - + + + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + k * f_vas_org * V_org - - - - - - + + + - - (V_kid * 1000 / 7)^0.75 * 1000 * 1E2 + + -(Q*HCT*C_bc) - + + + - - K_water_cell + + Q*HCT*C_bc - + + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + fu/K_cell_pls - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + P * P_int_cell_factor - - - - - - + + - - k * f_vas_org * V_org + + P * P_cell_int_factor - - - + + - - -(Q*(1-HCT)*C_pls) + + P_int_cell * SA - - - + + - - Q*(1-HCT)*C_pls + + P_cell_int * SA - - - + + - - -(Q*HCT*C_bc) + + fu/K_int_pls - - - + + - - Q*HCT*C_bc + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - + + + + + + - - Q*HCT*C_bc + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - + + + + + + - - -(MassTransferMucosaToPveBCRate) + + (V_kid * 1000 / 7)^0.75 * 1000 * 1E2 - + - - MassTransferMucosaToPveBCRate + + K_water_cell - + - - P_1 + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - + + + + + - - 0 - - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - - - - - - + + + + + - - -(DrugAbsorptionLumenToMucosaRate) + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - + + + + + - - DrugAbsorptionLumenToMucosaRate + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - + + + + + - - DrugAbsorptionLumenToMucosaRate + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - + + + + + - - F1*F2*F3 + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - + + + + + - - (1-F1)*F2*F3 + + -(OralApplicationsEnabled ? w*Drug : 0) - - - + + + - - F1*(1-F2)*F3 + + OralApplicationsEnabled ? w*Drug : 0 - - - + + + - - F1*F2*(1-F3) + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - + + + + + - - (1-F1)*(1-F2)*F3 + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - + + + + + - - (1-F1)*F2*(1-F3) + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - + + + + + - - F1*(1-F2)*(1-F3) + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - + + + + + - - (1-F1)*(1-F2)*(1-F3) + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - + + + + + - - 0 - - - P_1 + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - + + + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - + + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - + + + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + Q*HCT*C_bc - - - - - - - - - - - - - + + + - - (1-F1)*F2*F3 + + -(MassTransferMucosaToPveBCRate) - - - + - - (1-F1)*(1-F2)*(1-F3) + + MassTransferMucosaToPveBCRate - - - + - - F1*(1-F2)*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - (1-F1)*F2*(1-F3) + + -(MassTransferMucosaToPvePlasmaRate) - - - + - - (1-F1)*(1-F2)*F3 + + MassTransferMucosaToPvePlasmaRate - - - + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + (1-F1)*F2*F3 - - - - - - - - - - - - - + + + - + F1*(1-F2)*F3 - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + F1*F2*(1-F3) - - - - + + + - - F1*F2*F3 + + (1-F1)*(1-F2)*F3 - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + (1-F1)*F2*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + F1*(1-F2)*(1-F3) - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - K_water_cell + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - + + + + - - K_cell_pls + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - + + + + - - F1*F2*(1-F3) + + F1*F2*F3 - - - + + + - - -(DrugAbsorptionLumenToMucosaRate) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - + + + + - - DrugAbsorptionLumenToMucosaRate + + F1*(1-F2)*F3 - + + + - - DrugAbsorptionLumenToMucosaRate + + F1*F2*(1-F3) - + + + - - Q*(1-HCT)*C_pls + + (1-F1)*(1-F2)*F3 - - - + + + - - -(MassTransferMucosaToPvePlasmaRate) + + (1-F1)*F2*(1-F3) - + + + - - MassTransferMucosaToPvePlasmaRate + + F1*(1-F2)*(1-F3) - + + + - - Q*HCT*C_bc + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - -(MassTransferMucosaToPveBCRate) + + 0 + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - + + + + - - MassTransferMucosaToPveBCRate + + (1-F1)*F2*F3 - + + + - - -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + F1*F2*F3 - - - - - + + + - - (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - + + + + + + + + + + + + + - - -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - + + + + + + + + + + + + + + + + + K_cell_pls + + - - (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + K_water_cell - - - - - + - - MAbs_duo + MAbs_uje + MAbs_lje + MAbs_uil + MAbs_lil + MAbs_cae + MAbs_colasc + MAbs_coltrans + MAbs_coldesc + MAbs_colsigm + MAbs_rect + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - - - - - - - - + + + + - - -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - + + + + - - (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + P_1 - - - - - + - - -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + -(DrugAbsorptionLumenToMucosaRate) - - - - - + - - (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + DrugAbsorptionLumenToMucosaRate - - - - - + - - -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + DrugAbsorptionLumenToMucosaRate - - - - - + - - (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + 0 + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - - - + + + + + + + + + + - - -(OralApplicationsEnabled ? w*Drug : 0) + + P_1 - - - + - - OralApplicationsEnabled ? w*Drug : 0 + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + DrugAbsorptionLumenToMucosaRate - - - - - + - - (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + DrugAbsorptionLumenToMucosaRate - - - - - + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - - - - - -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - - + + + + + - - (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + MAbs_duo + MAbs_uje + MAbs_lje + MAbs_uil + MAbs_lil + MAbs_cae + MAbs_colasc + MAbs_coltrans + MAbs_coldesc + MAbs_colsigm + MAbs_rect - - - - - + + + + + + + + + + + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) - - - - - + + + + + - + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 - - - - - + + + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + -(Q*HCT*C_bc) - - - - + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + Q*HCT*C_bc - - - - - - + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + P_cell_int * SA - - - - - - + + - - k * f_vas_org * V_org + + P * P_int_cell_factor - - - + + - - -(Q*HCT*C_bc) + + P * P_cell_int_factor - - - + + - - Q*HCT*C_bc + + P_int_cell * SA - - - + + - - -(Q*(1-HCT)*C_pls) + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - + + + + + + - - Q*(1-HCT)*C_pls + + fu/K_cell_pls - - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + fu/K_int_pls - - - - - - + + - - fu/K_cell_pls + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - + + + + + + - - P_cell_int * SA + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - + + + + + + - - P_int_cell * SA + + (V_sto * 1000 / 1.1)^0.75 * 1000 * 1E2 - - + - - P * P_int_cell_factor + + -(Q*(1-HCT)*C_pls) - - + + + - - P * P_cell_int_factor + + Q*(1-HCT)*C_pls - - + + + - - fu/K_int_pls + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - + + + + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - + + + + + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - - + + + + - - (V_sto * 1000 / 1.1)^0.75 * 1000 * 1E2 + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - + + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - - + + + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - - + + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + k * f_vas_org * V_org - - - - + + + - - P_1 + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - + + + + + + + + + + - + 0 - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + P_1 - - - - - - - - - - + - + -(DrugAbsorptionLumenToMucosaRate) - + - + DrugAbsorptionLumenToMucosaRate - + - + DrugAbsorptionLumenToMucosaRate - - - - - (1-F1)*F2*F3 - - - - - - - - F1*(1-F2)*(1-F3) - - - - - - - - F1*F2*(1-F3) - - - - + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + F1*F2*F3 - - - + + + - + (1-F1)*F2*F3 - - - + + + - - F1*(1-F2)*F3 + + F1*F2*(1-F3) - - - + + + - - F1*F2*(1-F3) + + F1*(1-F2)*F3 - - - + + + - - (1-F1)*(1-F2)*F3 + + (1-F1)*F2*(1-F3) - - - + + + - - (1-F1)*F2*(1-F3) + + F1*(1-F2)*(1-F3) - - - + + + - - P_1 + + (1-F1)*(1-F2)*(1-F3) - + + + - + 0 - - (1-F1)*(1-F2)*(1-F3) + + P_1 - - - + - - F1*F2*F3 + + F1*(1-F2)*F3 - - - + + + - - F1*(1-F2)*F3 + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + + + + + (1-F1)*(1-F2)*F3 + + + + - + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - + + + + + + + + + + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + F1*F2*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls - - - - + - + + K_water_cell + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - K_water_cell + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - + + + + - - K_cell_pls + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - + + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + F1*F2*F3 - - - - - - - - - - - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + (1-F1)*F2*F3 - - - - - - - - - - - - - + + + - + -(DrugAbsorptionLumenToMucosaRate) - + - + DrugAbsorptionLumenToMucosaRate - + - + DrugAbsorptionLumenToMucosaRate - + - - Q*(1-HCT)*C_pls + + Q*HCT*C_bc - - - + + + - - -(MassTransferMucosaToPvePlasmaRate) + + -(MassTransferMucosaToPveBCRate) - + - - MassTransferMucosaToPvePlasmaRate + + MassTransferMucosaToPveBCRate - + - - Q*HCT*C_bc + + Q*(1-HCT)*C_pls - - - + + + - - -(MassTransferMucosaToPveBCRate) + + -(MassTransferMucosaToPvePlasmaRate) - + - - MassTransferMucosaToPveBCRate + + MassTransferMucosaToPvePlasmaRate - + - + -((1-fractQ)*Q*(1-HCT)*C) - - - - + + + + - + (1-fractQ)*Q*(1-HCT)*C - - - - + + + + - - P * P_cell_int_factor + + Q*(1-HCT)*C_pls - - + + + - - P_int_cell * SA + + -(MassTransferIntestineToMucosaPlasmaRate) - - + - - P_cell_int * SA + + MassTransferIntestineToMucosaPlasmaRate - - + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + Q*HCT*C_bc - - - - - - + + + - - fu/K_cell_pls + + -(MassTransferIntestineToMucosaBCRate) - - + - - P * P_int_cell_factor + + MassTransferIntestineToMucosaBCRate - - + - - fu/K_int_pls + + Q*(1-HCT)*C_pls - - + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + -(MassTransferIntestineToMucosaPlasmaRate) - - - - - - + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + MassTransferIntestineToMucosaPlasmaRate - - - - - - + - - ((V_sin-V_Mucosa) * 1000 / 11.1)^0.75 * 1000 * 1E2 + + Q*HCT*C_bc - - + + + - - Q*(1-HCT)*C_pls + + -(MassTransferIntestineToMucosaBCRate) - - - + - - -(MassTransferIntestineToMucosaPlasmaRate) + + MassTransferIntestineToMucosaBCRate - + - - MassTransferIntestineToMucosaPlasmaRate + + Q*(1-HCT)*C_pls - + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + -(MassTransferIntestineToMucosaPlasmaRate) - - - - + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + MassTransferIntestineToMucosaPlasmaRate - - - - - - + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + Q*HCT*C_bc - - - - - - + + + - - k * f_vas_org * (V_org-V_Mucosa) + + -(MassTransferMucosaToPveBCRate) - - - - + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + MassTransferMucosaToPveBCRate - - - - - - - + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - - - - - + + + + + + + + + + - - HCT * A_to_V_bc * 0.6 * (V-V_Mucosa) * f_vas + + 0 + + + P_1 - - - - - + - - Q*(1-HCT)*C_pls + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - -(MassTransferIntestineToMucosaPlasmaRate) + + DrugAbsorptionLumenToMucosaRate - + - - MassTransferIntestineToMucosaPlasmaRate + + DrugAbsorptionLumenToMucosaRate - + - - Q*HCT*C_bc + + F1*(1-F2)*F3 - - - + + + - - -(MassTransferIntestineToMucosaBCRate) + + F1*F2*(1-F3) - + + + - - MassTransferIntestineToMucosaBCRate + + (1-F1)*(1-F2)*F3 - + + + - - -((1-fractQ)*Q*HCT*C) + + (1-F1)*F2*(1-F3) - - - - + + + - - (1-fractQ)*Q*HCT*C + + F1*(1-F2)*(1-F3) - - - - + + + - - Q*HCT*C_bc + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - -(MassTransferMucosaToPveBCRate) + + 0 + + + P_1 - + - - MassTransferMucosaToPveBCRate + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - + + + + - - Q*(1-HCT)*C_pls + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - -(MassTransferMucosaToPvePlasmaRate) + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - + + + + + + + + + + + + + - - MassTransferMucosaToPvePlasmaRate + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - + + + + + + + + + + + + + - - Q*HCT*C_bc + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls - - - + - - -(MassTransferIntestineToMucosaBCRate) + + K_water_cell - + - - MassTransferIntestineToMucosaBCRate + + (1-F1)*F2*F3 - + + + - - Q*(1-HCT)*C_pls + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + F1*F2*F3 - + + + - - MassTransferIntestineToMucosaPlasmaRate + + F1*F2*F3 - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + (1-F1)*F2*F3 - - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - - - K_cell_pls + + F1*(1-F2)*F3 - + + + - - K_water_cell + + F1*F2*(1-F3) - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + (1-F1)*(1-F2)*F3 - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*F2*(1-F3) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + F1*(1-F2)*(1-F3) - - - - + + + - - F1*F2*F3 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - (1-F1)*F2*F3 + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - F1*(1-F2)*F3 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - F1*F2*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - (1-F1)*F2*(1-F3) + + DrugAbsorptionLumenToMucosaRate - - - + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + DrugAbsorptionLumenToMucosaRate - - - - - - - - - - - - - + - - F1*F2*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - P_1 + + -(MassTransferIntestineToMucosaPlasmaRate) - + - - 0 - - - (1-F1)*(1-F2)*(1-F3) + + MassTransferIntestineToMucosaPlasmaRate - - - + - - F1*(1-F2)*(1-F3) + + Q*HCT*C_bc - - - + + + - - F1*(1-F2)*(1-F3) + + -(MassTransferIntestineToMucosaBCRate) - - - + - - (1-F1)*(1-F2)*F3 + + MassTransferIntestineToMucosaBCRate - - - + - - (1-F1)*(1-F2)*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - F1*(1-F2)*F3 + + -(MassTransferMucosaToPvePlasmaRate) - - - + - - (1-F1)*F2*F3 + + MassTransferMucosaToPvePlasmaRate - - - + - - F1*F2*F3 + + Q*(1-HCT)*C_pls - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + -(MassTransferIntestineToMucosaPlasmaRate) - - - - + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + MassTransferIntestineToMucosaPlasmaRate - - - - + - - (1-F1)*F2*(1-F3) + + Q*HCT*C_bc - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - - - -(DrugAbsorptionLumenToMucosaRate) + + -(MassTransferIntestineToMucosaBCRate) - + - - DrugAbsorptionLumenToMucosaRate + + MassTransferIntestineToMucosaBCRate - + - - DrugAbsorptionLumenToMucosaRate + + P * P_int_cell_factor - + + - - Q*HCT*C_bc + + P * P_cell_int_factor - - - + + - - -(MassTransferIntestineToMucosaBCRate) + + P_int_cell * SA - + + - - MassTransferIntestineToMucosaBCRate + + P_cell_int * SA - + + - - P_1 + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - + + + + + + - - 0 - - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + fu/K_cell_pls - - - - - - - - - - + + - - -(DrugAbsorptionLumenToMucosaRate) + + fu/K_int_pls - + + - - DrugAbsorptionLumenToMucosaRate + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - + + + + + + - - DrugAbsorptionLumenToMucosaRate + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - + + + + + + - - Q*HCT*C_bc + + ((V_sin-V_Mucosa) * 1000 / 11.1)^0.75 * 1000 * 1E2 - - - + + - - -(MassTransferIntestineToMucosaBCRate) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - + + + + + + + - - MassTransferIntestineToMucosaBCRate + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - + + + + + + + - - Q*(1-HCT)*C_pls + + HCT * A_to_V_bc * 0.6 * (V-V_Mucosa) * f_vas - - - + + + + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + -((1-fractQ)*Q*HCT*C) - + + + + - - MassTransferIntestineToMucosaPlasmaRate + + (1-fractQ)*Q*HCT*C - + + + + - + Q*HCT*C_bc - - - + + + - + -(MassTransferIntestineToMucosaBCRate) - + - + MassTransferIntestineToMucosaBCRate - + - - Q*(1-HCT)*C_pls + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - + + + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - + + + + + + - - MassTransferIntestineToMucosaPlasmaRate + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - + + + + + + - - Q*(1-HCT)*C_pls + + k * f_vas_org * (V_org-V_Mucosa) - - - + + + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + Q*HCT*C_bc - + + + - - MassTransferIntestineToMucosaPlasmaRate + + -(MassTransferIntestineToMucosaBCRate) - + - + + MassTransferIntestineToMucosaBCRate + + + + + Q*(1-HCT)*C_pls - - - + + + - + -(MassTransferIntestineToMucosaPlasmaRate) - + - + MassTransferIntestineToMucosaPlasmaRate - + - + Q*HCT*C_bc - - - + + + - + -(MassTransferIntestineToMucosaBCRate) - + - + MassTransferIntestineToMucosaBCRate - + - + Q*(1-HCT)*C_pls - - - + + + - + -(MassTransferIntestineToMucosaPlasmaRate) - + - + MassTransferIntestineToMucosaPlasmaRate - + - - Q*HCT*C_bc + + Q*(1-HCT)*C_pls - - - + + + - - -(MassTransferIntestineToMucosaBCRate) + + -(MassTransferIntestineToMucosaPlasmaRate) - + - - MassTransferIntestineToMucosaBCRate + + MassTransferIntestineToMucosaPlasmaRate - + - - Q*(1-HCT)*C_pls + + Q*HCT*C_bc - - - + + + - - -(MassTransferIntestineToMucosaPlasmaRate) + + -(MassTransferIntestineToMucosaBCRate) - + - - MassTransferIntestineToMucosaPlasmaRate + + MassTransferIntestineToMucosaBCRate - + - + Q*HCT*C_bc - - - + + + - + -(MassTransferIntestineToMucosaBCRate) - + - + MassTransferIntestineToMucosaBCRate - + - - Q*HCT*C_bc + + Q*(1-HCT)*C_pls - - - + + + - - -(MassTransferIntestineToMucosaBCRate) + + -(MassTransferIntestineToMucosaPlasmaRate) - + - - MassTransferIntestineToMucosaBCRate + + MassTransferIntestineToMucosaPlasmaRate - + - + Q*(1-HCT)*C_pls - - - + + + - + -(MassTransferIntestineToMucosaPlasmaRate) - + - + MassTransferIntestineToMucosaPlasmaRate - + - + Q*HCT*C_bc - - - + + + - + -(MassTransferIntestineToMucosaBCRate) - + - + MassTransferIntestineToMucosaBCRate - + - + Q*(1-HCT)*C_pls - - - + + + - + -(MassTransferIntestineToMucosaPlasmaRate) - + - + MassTransferIntestineToMucosaPlasmaRate - + - + Q*HCT*C_bc - - - + + + - + -(MassTransferIntestineToMucosaBCRate) - + - + MassTransferIntestineToMucosaBCRate - + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + -((1-fractQ)*Q*(1-HCT)*C) - - - - - - - + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + (1-fractQ)*Q*(1-HCT)*C - - - - - - - + + + + - - HCT * A_to_V_bc * 0.6 * (V-V_Mucosa) * f_vas + + -((1-fractQ)*Q*HCT*C) - - - - - + + + + - - P * P_int_cell_factor + + (1-fractQ)*Q*HCT*C - - + + + + - - P * P_cell_int_factor + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - + + + + - - P_int_cell * SA + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - + + + + + + - - P_cell_int * SA + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - + + + + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + k * f_vas_org * (V_org-V_Mucosa) - - - - - - + + + + - - fu/K_cell_pls + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - + + + + + + + - - fu/K_int_pls + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - + + + + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + HCT * A_to_V_bc * 0.6 * (V-V_Mucosa) * f_vas - - - - - - + + + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - - ((V_lin-V_Mucosa) * 1000 / 11.1)^0.75 * 1000 * 1E2 + + P * P_int_cell_factor - - + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + P * P_cell_int_factor - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + P_int_cell * SA - - - - - - + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + P_cell_int * SA - - - - - - + + - - k * f_vas_org * (V_org-V_Mucosa) + + fu/K_cell_pls - - - - + + - - -((1-fractQ)*Q*(1-HCT)*C) + + fu/K_int_pls - - - - + + - - (1-fractQ)*Q*(1-HCT)*C + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - + + + + + + - - -((1-fractQ)*Q*HCT*C) + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - + + + + + + - - (1-fractQ)*Q*HCT*C + + ((V_lin-V_Mucosa) * 1000 / 11.1)^0.75 * 1000 * 1E2 - - - - + + - + k * f_vas_org * V_org - - + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - - - - (V_liv * 1000 / 10)^0.75 * 82 * 1E2 - - + + + + - + -(EHC_Active ? ln(2) / EHC_Halftime * M * EHC_EjectionFraction : 0) - - - - + + + + - + EHC_Active ? ln(2) / EHC_Halftime * M * EHC_EjectionFraction : 0 - - - - - - - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - - - - - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - - + + + + - - SA_pls_int * (IsLiverZonated? f_periportal : 1) + + (V_liv * 1000 / 10)^0.75 * 82 * 1E2 - - - + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + SA_pls_bc * (IsLiverZonated? f_periportal : 1) - - - + + + - - P * P_int_cell_factor + + fu/K_cell_pls - - + + - - P * P_cell_int_factor + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - - P_int_cell * SA + + P_cell_int * SA - - + + - - P_cell_int * SA + + P_int_cell * SA - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P * P_cell_int_factor - - - - - - + + - - fu/K_cell_pls + + P * P_int_cell_factor - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + SA_int_cell * (IsLiverZonated? f_periportal : 1) - - - - - - - P * P_int_cell_factor - - - - - - - P * P_cell_int_factor - - - - - - - P_cell_int * SA - - - - - - - fu/K_cell_pls - - - - - - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - - - - - - P_int_cell * SA - - - + + + - - fu/K_int_pls + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - - SA_int_cell * (IsLiverZonated? 1-f_periportal : 0) + + SA_pls_int * (IsLiverZonated? f_periportal : 1) - - - + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + SA_pls_int * (IsLiverZonated? 1-f_periportal : 0) - - - + + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + SA_pls_bc * (IsLiverZonated? 1-f_periportal : 0) - - - + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + P * P_int_cell_factor + + + + + + + P_cell_int * SA - - - - + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + P * P_cell_int_factor - - - - - - + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + P_int_cell * SA - - - - - - + + - - k * f_vas_org * V_org + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - + + + + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + fu/K_cell_pls - - - - - - - + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + fu/K_int_pls - - - - - - - + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - + + + + + + - - -(Q*(1-HCT)*C_pls) + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - + + + + + + - - Q*(1-HCT)*C_pls + + SA_int_cell * (IsLiverZonated? 1-f_periportal : 0) - - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + -(Q*HCT*C_bc) - - - - - - + + + - - fu/K_cell_pls + + Q*HCT*C_bc - - + + + - + P * P_int_cell_factor - - + + - + P * P_cell_int_factor - - + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + + + + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + + + + + + + + + + fu/K_cell_pls + + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_lng * 1000 / 2.2)^0.75 * 0.096 * 1E2 - + - - -(Q*HCT*C_bc) + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - + + + + - - Q*HCT*C_bc + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - + + + + + + - + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - -(Q*HCT*C_bc) + + -(Q*(1-HCT)*C_pls) - - - + + + - - Q*HCT*C_bc + + Q*(1-HCT)*C_pls - - - + + + - - P * P_int_cell_factor + + P_int_cell * SA - - + + - + P * P_cell_int_factor - - - - - - P_int_cell * SA - - - + + - + P_cell_int * SA - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - + fu/K_cell_pls - - + + - + + P * P_int_cell_factor + + + + + + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_mus * 1000 / 110.1)^0.75 * 7.54 * 1E2 - + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - - - - -(Q*(1-HCT)*C_pls) - - - - + + + + - - Q*(1-HCT)*C_pls + + -(Q*HCT*C_bc) - - - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + Q*HCT*C_bc - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(Q*HCT*C_bc) - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + Q*HCT*C_bc - - - - + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - -(Q*(1-HCT)*C_pls) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - + + + + + + + - - Q*(1-HCT)*C_pls + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - + + + + + + + - - P_cell_int * SA + + HCT * A_to_V_bc * 0.6 * V * f_vas - - + + + + - + P * P_int_cell_factor - - + + + + + + P * P_cell_int_factor + + + - + P_int_cell * SA - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - + fu/K_cell_pls - - + + - - P * P_cell_int_factor + + P_cell_int * SA - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_pan * 1000 / 1.3)^0.75 * 1000 * 1E2 - + - - -(Q*HCT*C_bc) + + -(Q*(1-HCT)*C_pls) - - - + + + - - Q*HCT*C_bc + + Q*(1-HCT)*C_pls - - - + + + - + Q*(1-HCT)*C_pls - - - + + + - + -(MassTransferMucosaToPvePlasmaRate) - + - + MassTransferMucosaToPvePlasmaRate - + - + Q*HCT*C_bc - - - + + + - + -(MassTransferMucosaToPveBCRate) - + - + MassTransferMucosaToPveBCRate - + - - 0 - - - 0 - - + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - - - - - - - - + + + + + + + + + + - - F1*(1-F2)*(1-F3) - - - - - - - - (1-F1)*(1-F2)*(1-F3) - - - - - - - + 0 - - P_1 - - - - - - (1-F1)*(1-F2)*F3 - - - - - - - - F1*F2*(1-F3) - - - - - + + 0 - - F1*F2*(1-F3) + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - + + + + + + + + + + + + + - - K_cell_pls + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - + + + + + + + + + + + + + - - K_water_cell + + K_cell_pls - + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - - - - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - + F1*F2*F3 - - - + + + - - (1-F1)*F2*(1-F3) + + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - + + F1*F2*(1-F3) + + + + + + + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + K_water_cell - - - - + - - F1*F2*F3 + + (1-F1)*F2*F3 - - - + + + - - (1-F1)*F2*F3 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - + F1*(1-F2)*F3 - - - + + + - - (1-F1)*F2*F3 + + F1*F2*(1-F3) - - - + + + - - -(DrugAbsorptionLumenToMucosaRate) + + (1-F1)*(1-F2)*F3 - + + + - - DrugAbsorptionLumenToMucosaRate + + (1-F1)*F2*(1-F3) - + + + - - DrugAbsorptionLumenToMucosaRate + + F1*(1-F2)*(1-F3) - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (1-F1)*(1-F2)*(1-F3) - - - - - - - + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + 0 + + + P_1 - - - - - - - + - - HCT * A_to_V_bc * 0.6 * V + + F1*F2*F3 - - - + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + -(DrugAbsorptionLumenToMucosaRate) - - - - - - - + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + DrugAbsorptionLumenToMucosaRate - - - - - - - + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + DrugAbsorptionLumenToMucosaRate - - - - + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - + + + + + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - + + + + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + HCT * A_to_V_bc * 0.6 * V - - - - - - + + + - - k * f_vas_org * V_org + + -(Q*(1-HCT)*C_pls) - - - + + + - - -(Q*HCT*C_bc) + + Q*(1-HCT)*C_pls - - - + + + - - Q*HCT*C_bc + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - + + + + - - -(Q*(1-HCT)*C_pls) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - + + + + + + - - Q*(1-HCT)*C_pls + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - + + + + + + - - fu/K_cell_pls + + k * f_vas_org * V_org - - + + + - + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + + + + + + + + + P * P_int_cell_factor - - + + - + P * P_cell_int_factor - - + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + fu/K_cell_pls - - - - - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_skn * 1000 / 43.4)^0.75 * 0.12 * 1E2 - - - - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - - + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + -(Q*HCT*C_bc) - - - - - - + + + - - k * f_vas_org * V_org + + Q*HCT*C_bc - - - + + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - + -(Q*(1-HCT)*C_pls) - - - + + + - + Q*(1-HCT)*C_pls - - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P_cell_int * SA - - - - - - + + - - fu/K_cell_pls + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - - P * P_int_cell_factor + + fu/K_cell_pls - - + + - + P * P_cell_int_factor - - + + - - P_int_cell * SA + + P * P_int_cell_factor - - + + - - P_cell_int * SA + + P_int_cell * SA - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + (V_spl * 1000 / 1.3)^0.75 * 1000 * 1E2 - + - + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - - - - - R * fu - - - + + + - - 1 + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - + + + + + + + - - -(fu * (C_pls_art - C_slv / K_slv_pls) * Q_slv) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - + + + + + + + - - fu * (C_pls_art - C_slv / K_slv_pls) * Q_slv + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - + + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - - - - - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - - - - - - HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - - - - - P * P_int_cell_factor * P_int_scalefactor - - - - - - - - P * P_cell_int_factor * P_int_scalefactor - - - - - - - - P_int_cell * SA - - - - - - - P_cell_int * SA + + R * fu - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + 1 - - - - - - + + + + + - - fu/K_cell_pls + + -(fu * (C_pls_art - C_slv / K_slv_pls) * Q_slv) - - + + + + + - - fu/K_int_pls + + fu * (C_pls_art - C_slv / K_slv_pls) * Q_slv - - + + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - + + + + + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - + + + + + + + - - Aeff / MicrovilliFactor + + HCT * A_to_V_bc * 0.6 * V * f_vas - - + + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - + + fu/K_cell_pls + + + + + + P * P_int_cell_factor * P_int_scalefactor - - - + + + - + P * P_cell_int_factor * P_int_scalefactor - - - + + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - - - - - fu/K_cell_pls - - - + + + + + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - - - - P * P_cell_int_factor * P_int_scalefactor - - - - + + + + - + P * P_int_cell_factor * P_int_scalefactor - - - + + + - - P_int_cell * SA + + P * P_cell_int_factor * P_int_scalefactor - - + + + - + P_cell_int * SA - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - + fu/K_cell_pls - - + + + + + + P_int_cell * SA + + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - - + + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - + + + + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + k * f_vas_org * V_org - - - - + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - + + + + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - + + + + + + + - - k * f_vas_org * V_org + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - + + + + - + P * P_int_cell_factor * P_int_scalefactor - - - + + + - + P * P_cell_int_factor * P_int_scalefactor - - - + + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + fu/K_cell_pls - - - - - - + + - - fu/K_cell_pls + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - - - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - - + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - + + + + + + - - P * P_int_cell_factor * P_int_scalefactor + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - + + + + + + - - P * P_cell_int_factor * P_int_scalefactor + + k * f_vas_org * V_org - - - + + + - + P_int_cell * SA - - + + - + P_cell_int * SA - - + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - + fu/K_cell_pls - - + + - + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - + + + + + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - + + + + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - - - + + + + - - k * f_vas_org * V_org + + P * P_int_cell_factor * P_int_scalefactor - - - + + + - + P * P_cell_int_factor * P_int_scalefactor - - - - - - - fu/K_cell_pls - - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P_int_cell * SA - - - - - - + + - - P_int_cell * SA + + P_cell_int * SA - - + + - - P * P_int_cell_factor * P_int_scalefactor + + fu/K_cell_pls - - - + + - - P_cell_int * SA + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - + + + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - - + + + + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - + + + + + + - - fu/K_cell_pls + + k * f_vas_org * V_org - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P * P_int_cell_factor * P_int_scalefactor - - - - - - + + + - - P_cell_int * SA + + P * P_cell_int_factor * P_int_scalefactor - - + + + - + P_int_cell * SA - - + + - - P * P_int_cell_factor * P_int_scalefactor + + P_cell_int * SA - - - + + - - P * P_cell_int_factor * P_int_scalefactor + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + + + + + + + + + + fu/K_cell_pls - - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - - - - - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - + + + + + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - + + + + + + + - - k * f_vas_org * V_org + + HCT * A_to_V_bc * 0.6 * V * f_vas - - - + + + + - - fu/K_cell_pls + + P_cell_int * SA - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P * P_int_cell_factor * P_int_scalefactor - - - - - - + + + - - P_cell_int * SA + + P_int_cell * SA - - + + - - P_int_cell * SA + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - - P * P_int_cell_factor * P_int_scalefactor + + fu/K_cell_pls - - - + + - + P * P_cell_int_factor * P_int_scalefactor - - - + + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - - fu/K_cell_pls + + P * P_int_cell_factor * P_int_scalefactor - - + + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + P * P_cell_int_factor * P_int_scalefactor - - - - - - + + + - - P_cell_int * SA + + P_int_cell * SA - - + + - - P_int_cell * SA + + P_cell_int * SA - - + + - - P * P_cell_int_factor * P_int_scalefactor + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - + + + + + + - - P * P_int_cell_factor * P_int_scalefactor + + fu/K_cell_pls - - - + + - + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - - (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + P * P_int_cell_factor * P_int_scalefactor - - - - + + + - - -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + P * P_cell_int_factor * P_int_scalefactor - - - - - - + + + - - fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + P_int_cell * SA - - - - - - + + - - k * f_vas_org * V_org + + P_cell_int * SA - - - + + - - P_cell_int * SA + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - + + + + + + - + fu/K_cell_pls - - + + - - P_int_cell * SA + + fu/K_int_pls - - + + - - (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - - P * P_cell_int_factor * P_int_scalefactor + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - + + + + + + - - P * P_int_cell_factor * P_int_scalefactor + + Aeff / MicrovilliFactor - - - + + - - fu/K_int_pls + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - + + + + - - -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - - K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - - Aeff / MicrovilliFactor + + k * f_vas_org * V_org - - + + + - + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - - - - - + + + + + + + - + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - - - - - - - + + + + + + + - + HCT * A_to_V_bc * 0.6 * V * f_vas - - - - + + + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + P_cell_int * SA - - - - - - - + + - - SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + P * P_cell_int_factor * P_int_scalefactor - - - - - - - + + + - - HCT * A_to_V_bc * 0.6 * V * f_vas + + P_int_cell * SA + + + + + + + P * P_int_cell_factor * P_int_scalefactor - - - - + + + - + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu - - - - - - + + + + + + - + fu/K_cell_pls - - + + - - P_int_cell * SA + + fu/K_int_pls - - + + - - P_cell_int * SA + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - + + + + + + - - P * P_cell_int_factor * P_int_scalefactor + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + fu/K_cell_pls + + + + + + + (f_water + f_lipids * 10^LogMA + f_proteins * KProt) * fu + + + + + + + - + P * P_int_cell_factor * P_int_scalefactor - - - + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + P_int_cell * SA + + + - + + P_cell_int * SA + + + + + + fu/K_int_pls - - + + - + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) - - - - - - + + + + + + - + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell - - - - - - + + + + + + - + Aeff / MicrovilliFactor - - + + - + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu - - - - + + + + - + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) - - - - - - + + + + + + - + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) - - - - - - + + + + + + - + k * f_vas_org * V_org - - + + - - Q*(1-HCT)*C_pls + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) - - - + + + + + + + - - -(MassTransferMucosaToPvePlasmaRate) + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) - + + + + + + + - - MassTransferMucosaToPvePlasmaRate + + HCT * A_to_V_bc * 0.6 * V * f_vas - + + + + - - Q*HCT*C_bc + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + + + + - - -(MassTransferMucosaToPveBCRate) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - + + + + + + + + + + + + + - - MassTransferMucosaToPveBCRate + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - + + + + + + + + + + + + + - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + K_cell_pls - - - - - - - - - - + - - 0 - - - 0 - - - 0 - - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + K_water_cell - - - - + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - - F1*F2*F3 + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - + (1-F1)*F2*F3 - - - - - - - F1*(1-F2)*F3 - - - - - - - - F1*F2*(1-F3) - - - - + + + - - (1-F1)*(1-F2)*F3 + + F1*F2*F3 - - - + + + - - (1-F1)*F2*(1-F3) + + (1-F1)*F2*F3 - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + F1*(1-F2)*F3 - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + F1*F2*(1-F3) - - - + + + - - F1*(1-F2)*(1-F3) + + (1-F1)*(1-F2)*F3 - - - + + + - - P_1 + + (1-F1)*F2*(1-F3) - + + + - + F1*(1-F2)*(1-F3) - - - + + + - - K_cell_pls + + (1-F1)*(1-F2)*(1-F3) - + + + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - - - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - - - - - - - - - + + + + - - K_water_cell + + F1*F2*F3 - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*(1-F2)*F3 - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + F1*F2*(1-F3) - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + (1-F1)*(1-F2)*F3 - - - - + + + - - F1*F2*F3 + + (1-F1)*F2*(1-F3) - - - + + + - - (1-F1)*F2*F3 + + F1*(1-F2)*(1-F3) - - - + + + - - F1*(1-F2)*F3 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - F1*F2*(1-F3) - - - - - + + 0 - - (1-F1)*(1-F2)*F3 + + P_1 - - - + - - (1-F1)*F2*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - - - - - - - - - + + + + - + -(DrugAbsorptionLumenToMucosaRate) - + - + DrugAbsorptionLumenToMucosaRate - + - + DrugAbsorptionLumenToMucosaRate - + - + Q*(1-HCT)*C_pls - - - + + + - + -(MassTransferMucosaToPvePlasmaRate) - + - + MassTransferMucosaToPvePlasmaRate - + - + Q*HCT*C_bc - - - + + + - + -(MassTransferMucosaToPveBCRate) - + - + MassTransferMucosaToPveBCRate - + - - P_1 + + Q*HCT*C_bc - + + + - - 0 - - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + -(MassTransferMucosaToPveBCRate) - - - - - - - - - - + - - -(DrugAbsorptionLumenToMucosaRate) + + MassTransferMucosaToPveBCRate - + - - DrugAbsorptionLumenToMucosaRate + + Q*(1-HCT)*C_pls - + + + - - DrugAbsorptionLumenToMucosaRate + + -(MassTransferMucosaToPvePlasmaRate) - + - - -(Q*(1-HCT)*C_pls) + + MassTransferMucosaToPvePlasmaRate - - - + - - Q*(1-HCT)*C_pls + + F1*(1-F2)*F3 - - - + + + - - -(Q*(1-HCT)*C_pls) + + F1*F2*(1-F3) - - - + + + - - Q*(1-HCT)*C_pls - - - - - - - - -(Q*(1-HCT)*C_pls) - - - - - - - - Q*(1-HCT)*C_pls + + (1-F1)*(1-F2)*F3 - - - + + + - - -(Q*(1-HCT)*C_pls) + + (1-F1)*F2*(1-F3) - - - + + + - - Q*(1-HCT)*C_pls + + F1*(1-F2)*(1-F3) - - - + + + - - -(Q*(1-HCT)*C_pls) + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - Q*(1-HCT)*C_pls - - - - - + + 0 - - -(Q*(1-HCT)*C_pls) + + P_1 - - - + - - Q*(1-HCT)*C_pls + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - -(Q*(1-HCT)*C_pls) + + (1-F1)*F2*F3 - - - + + + - - Q*(1-HCT)*C_pls + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - -(Q*(1-HCT)*C_pls) + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - Q*(1-HCT)*C_pls + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + - - -(Q*(1-HCT)*C_pls) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - Q*(1-HCT)*C_pls + + + + + + + + + + + + + + + + + K_cell_pls - - - + - - -(Q*(1-HCT)*C_pls) + + K_water_cell - - - + - - Q*(1-HCT)*C_pls + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - -(Q*(1-HCT)*C_pls) + + F1*F2*F3 - - - + + + - - Q*(1-HCT)*C_pls + + (1-F1)*F2*F3 - - - + + + - - -(Q*(1-HCT)*C_pls) + + F1*(1-F2)*F3 - - - + + + - - Q*(1-HCT)*C_pls + + F1*F2*(1-F3) - - - + + + - - -(Q*HCT*C_bc) + + (1-F1)*(1-F2)*F3 - - - + + + - - Q*HCT*C_bc + + (1-F1)*F2*(1-F3) - - - + + + - - -(Q*HCT*C_bc) + + F1*(1-F2)*(1-F3) - - - + + + - - Q*HCT*C_bc + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - -(Q*HCT*C_bc) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - Q*HCT*C_bc + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - -(Q*HCT*C_bc) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - Q*HCT*C_bc + + F1*F2*F3 - - - + + + - - -(Q*HCT*C_bc) + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - Q*HCT*C_bc + + DrugAbsorptionLumenToMucosaRate - - - + - - -(Q*HCT*C_bc) + + DrugAbsorptionLumenToMucosaRate - - - + - - Q*HCT*C_bc + + (1-F1)*F2*F3 - - - + + + - - -(Q*(1-HCT)*C_pls) + + F1*F2*F3 - - - + + + - - Q*(1-HCT)*C_pls + + (1-F1)*F2*F3 - - - + + + - - K_cell_pls + + F1*(1-F2)*F3 - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + F1*F2*(1-F3) - - - - - - - - - - - - - + + + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + (1-F1)*(1-F2)*F3 - - - - - - - - - - - - - + + + - - K_water_cell + + (1-F1)*F2*(1-F3) - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + F1*(1-F2)*(1-F3) - - - - - - - - - - - - - + + + - - (1-F1)*F2*F3 + + (1-F1)*(1-F2)*(1-F3) - - - + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - - - - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - - + + + + - + F1*F2*F3 - - - + + + - - (1-F1)*F2*F3 + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - - - + + 0 - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + P_1 - - - - + - - (1-F1)*(1-F2)*(1-F3) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - - 0 - - - F1*F2*F3 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - F1*(1-F2)*(1-F3) + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - (1-F1)*F2*(1-F3) + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - (1-F1)*(1-F2)*F3 + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + - - F1*F2*(1-F3) + + K_cell_pls - - - + - - F1*(1-F2)*F3 + + K_water_cell - - - + - - P_1 + + -(DrugAbsorptionLumenToMucosaRate) - + - - -(DrugAbsorptionLumenToMucosaRate) + + DrugAbsorptionLumenToMucosaRate - + - + DrugAbsorptionLumenToMucosaRate - + - - DrugAbsorptionLumenToMucosaRate + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - + + + + + + + + + + - + + 0 + + + 0 + + Q*(1-HCT)*C_pls - - - + + + - + -(MassTransferMucosaToPvePlasmaRate) - + - + MassTransferMucosaToPvePlasmaRate - + - + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + 0 + + Q*HCT*C_bc - - - + + + - + -(MassTransferMucosaToPveBCRate) - + - + MassTransferMucosaToPveBCRate - + - - -(Q*HCT*C_bc) + + Q*(1-HCT)*C_pls - - - + + + - - Q*HCT*C_bc + + -(MassTransferMucosaToPvePlasmaRate) - - - + - - -(Q*HCT*C_bc) + + MassTransferMucosaToPvePlasmaRate - - - + - - Q*HCT*C_bc + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + + + + - - Q*(1-HCT)*C_pls + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - + + + + + + + + + + + + + - - -(MassTransferMucosaToPvePlasmaRate) + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - + + + + + + + + + + + + + - - MassTransferMucosaToPvePlasmaRate + + K_cell_pls - + - - Q*HCT*C_bc + + K_water_cell - - - + - - -(MassTransferMucosaToPveBCRate) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - + + + + - - MassTransferMucosaToPveBCRate + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - + + + + - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - 0 - - - 0 - - - F1*F2*F3 + + (1-F1)*F2*F3 - - - + + + - + F1*F2*F3 - - - + + + - + (1-F1)*F2*F3 - - - + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + F1*F2*F3 - - - - + + + - - (1-F1)*F2*F3 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - + F1*(1-F2)*F3 - - - + + + - + F1*F2*(1-F3) - - - + + + - + (1-F1)*(1-F2)*F3 - - - + + + - + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - + 0 - + P_1 - + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - - + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + -(DrugAbsorptionLumenToMucosaRate) - - - - + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + DrugAbsorptionLumenToMucosaRate - - - - + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + DrugAbsorptionLumenToMucosaRate - - - - - - - - - - - - - - - - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + Q*HCT*C_bc - - - - - - - - - - - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + -(MassTransferMucosaToPveBCRate) - - - - - - - - - - - - - + - - K_cell_pls + + MassTransferMucosaToPveBCRate - + - - K_water_cell + + Q*(1-HCT)*C_pls - + + + - - -(DrugAbsorptionLumenToMucosaRate) + + -(MassTransferMucosaToPvePlasmaRate) - + - - DrugAbsorptionLumenToMucosaRate + + MassTransferMucosaToPvePlasmaRate - + - - DrugAbsorptionLumenToMucosaRate + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - + + + + + + + + + + - + + 0 + + + 0 + + Q*HCT*C_bc - - - + + + - + -(MassTransferMucosaToPveBCRate) - + - + MassTransferMucosaToPveBCRate - + - - -(Q*HCT*C_bc) + + Q*(1-HCT)*C_pls - - - + + + - - Q*HCT*C_bc + + -(MassTransferMucosaToPvePlasmaRate) - - - + - - -(Q*HCT*C_bc) + + MassTransferMucosaToPvePlasmaRate - - - + - + Q*HCT*C_bc - - - + + + - - -(Q*HCT*C_bc) + + -(MassTransferMucosaToPveBCRate) - - - + - - Q*HCT*C_bc + + MassTransferMucosaToPveBCRate - - - + - - -(Q*HCT*C_bc) + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + - - Q*HCT*C_bc + + 0 + + + P_1 - - - + - - 0 + + -(DrugAbsorptionLumenToMucosaRate) + + + - - 0 + + DrugAbsorptionLumenToMucosaRate + + + - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + DrugAbsorptionLumenToMucosaRate - - - - - - - - - - + - + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + (1-F1)*F2*(1-F3) - - - + + + - + F1*(1-F2)*(1-F3) - - - + + + - + (1-F1)*(1-F2)*(1-F3) - - - + + + - + 0 - + P_1 - + - - F1*(1-F2)*F3 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - - + + + + - - K_water_cell + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + - + K_cell_pls - + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + K_water_cell - - - - - - - - - - - - - + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + (1-F1)*F2*F3 - - - - - - - - - - - - - - - - + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + F1*F2*F3 - - - - + + + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 - - - - - - - - - - - - - - - - - - F1*(1-F2)*(1-F3) + + F1*F2*F3 - - - + + + - + (1-F1)*F2*F3 - - - + + + - - F1*F2*F3 + + F1*(1-F2)*F3 - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + F1*F2*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + (1-F1)*(1-F2)*F3 - - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + (1-F1)*F2*(1-F3) - - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + F1*(1-F2)*(1-F3) - - - + + + - - F1*F2*(1-F3) + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - (1-F1)*F2*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - (1-F1)*(1-F2)*F3 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - F1*F2*(1-F3) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - + + + + - - F1*(1-F2)*F3 + + -(DrugAbsorptionLumenToMucosaRate) - - - + - - (1-F1)*F2*F3 + + DrugAbsorptionLumenToMucosaRate - - - + - - F1*F2*F3 + + DrugAbsorptionLumenToMucosaRate - - - + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - - + + + + + + + + + + - - -(DrugAbsorptionLumenToMucosaRate) + + 0 + + + 0 + + + F1*(1-F2)*(1-F3) - + + + - - DrugAbsorptionLumenToMucosaRate + + K_water_cell - + - - DrugAbsorptionLumenToMucosaRate + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - + + + + - - Q*(1-HCT)*C_pls + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - + + + + - - -(MassTransferMucosaToPvePlasmaRate) + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - + + + + - - MassTransferMucosaToPvePlasmaRate + + F1*F2*F3 - + + + - - Q*HCT*C_bc + + (1-F1)*F2*F3 - - - + + + - - -(MassTransferMucosaToPveBCRate) + + F1*(1-F2)*F3 - + + + - - MassTransferMucosaToPveBCRate + + F1*F2*(1-F3) - + + + - - 0 + + (1-F1)*(1-F2)*F3 + + + + + - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + (1-F1)*F2*(1-F3) - - - - - - - - - - + + + - - 0 + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + - - Q*(1-HCT)*C_pls + + (1-F1)*(1-F2)*(1-F3) - - - + + + - - -(MassTransferMucosaToPvePlasmaRate) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - + + + + - - MassTransferMucosaToPvePlasmaRate + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - + + + + - - 0 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + - - OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + F1*F2*F3 - - - - - - - - - - + + + - - 0 + + (1-F1)*F2*F3 + + + + + - + F1*(1-F2)*F3 - - - + + + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + (1-F1)*(1-F2)*F3 - - - - - - - - - - - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + K_cell_pls - - - - - - - - - - - - - - - - + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + (1-F1)*F2*(1-F3) + + + + - - K_cell_pls + + F1*F2*(1-F3) - + + + - - K_water_cell + + F1*(1-F2)*(1-F3) - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + (1-F1)*(1-F2)*(1-F3) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + 0 + + + P_1 - - - - + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + -(DrugAbsorptionLumenToMucosaRate) - - - - + - - (1-F1)*F2*F3 + + DrugAbsorptionLumenToMucosaRate - - - + - - F1*F2*(1-F3) + + DrugAbsorptionLumenToMucosaRate - - - + - - (1-F1)*(1-F2)*F3 + + -(Q*HCT*C_bc) - - - + + + - - (1-F1)*F2*(1-F3) + + Q*HCT*C_bc - - - + + + - - F1*(1-F2)*(1-F3) + + -(Q*HCT*C_bc) - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + Q*HCT*C_bc - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + -(Q*(1-HCT)*C_pls) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + Q*(1-HCT)*C_pls - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + -(Q*(1-HCT)*C_pls) - - - - + + + - - F1*F2*F3 + + Q*(1-HCT)*C_pls - - - + + + - - (1-F1)*F2*F3 + + -(Q*(1-HCT)*C_pls) - - - + + + - - F1*F2*F3 + + Q*(1-HCT)*C_pls - - - + + + - - (1-F1)*(1-F2)*F3 + + -(Q*(1-HCT)*C_pls) - - - + + + - - F1*(1-F2)*F3 + + Q*(1-HCT)*C_pls - - - + + + - - (1-F1)*F2*(1-F3) + + -(Q*(1-HCT)*C_pls) - - - + + + - - F1*(1-F2)*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + -(Q*(1-HCT)*C_pls) - - - + + + - - 0 - - - P_1 + + Q*(1-HCT)*C_pls - + + + - - F1*F2*(1-F3) + + -(Q*(1-HCT)*C_pls) - - - + + + - - -(DrugAbsorptionLumenToMucosaRate) + + Q*(1-HCT)*C_pls - + + + - - DrugAbsorptionLumenToMucosaRate + + -(Q*(1-HCT)*C_pls) - + + + - - DrugAbsorptionLumenToMucosaRate + + Q*(1-HCT)*C_pls - + + + - + -(Q*HCT*C_bc) - - - + + + - + Q*HCT*C_bc - - - + + + - - (1-F1)*F2*(1-F3) + + -(Q*(1-HCT)*C_pls) - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + Q*(1-HCT)*C_pls - - - - + + + - - (1-F1)*(1-F2)*F3 + + -(Q*(1-HCT)*C_pls) - - - + + + - - F1*F2*(1-F3) + + Q*(1-HCT)*C_pls - - - + + + - - F1*(1-F2)*F3 + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 - - - + + + + + + + + + + - - (1-F1)*F2*F3 + + 0 + + + 0 + + + -(Q*(1-HCT)*C_pls) - - - + + + - - F1*F2*F3 + + Q*(1-HCT)*C_pls - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + -(Q*(1-HCT)*C_pls) - - - - + + + - - K_water_cell + + Q*(1-HCT)*C_pls - + + + - - K_cell_pls + + -(Q*HCT*C_bc) - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + Q*HCT*C_bc - - - - - - - - - - - - - + + + - - UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + -(Q*HCT*C_bc) - - - - - - - - - - - - - + + + - - OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + Q*HCT*C_bc - - - - - - - - - - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + -(Q*HCT*C_bc) - - - - + + + - - F1*(1-F2)*(1-F3) + + Q*HCT*C_bc - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + -(Q*HCT*C_bc) - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + Q*HCT*C_bc - - - + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + -(Q*HCT*C_bc) - - - - + + + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + Q*HCT*C_bc - - - - + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + -(Q*HCT*C_bc) - - - - + + + - - F1*F2*F3 + + Q*HCT*C_bc - - - + + + - - (1-F1)*F2*F3 + + -(Q*HCT*C_bc) - - - + + + - - F1*(1-F2)*F3 + + Q*HCT*C_bc - - - + + + - - F1*F2*(1-F3) + + -(Q*HCT*C_bc) - - - + + + - - (1-F1)*(1-F2)*F3 + + Q*HCT*C_bc - - - + + + - - F1*(1-F2)*(1-F3) + + -(Q*HCT*C_bc) - - - + + + - - 0 - - - P_1 + + Q*HCT*C_bc - + + + - - (1-F1)*F2*(1-F3) + + -(Q*HCT*C_bc) - - - + + + - - -(DrugAbsorptionLumenToMucosaRate) + + Q*HCT*C_bc - + + + - - DrugAbsorptionLumenToMucosaRate + + -(Q*(1-HCT)*C_pls) - + + + - - DrugAbsorptionLumenToMucosaRate + + Q*(1-HCT)*C_pls - + + + - - -(IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0) + + -(Q*(1-HCT)*C_pls) - - - - - + + + - - IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0 + + Q*(1-HCT)*C_pls - - - - - + + + - - -(IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0) + + -(Q*HCT*C_bc) - - - - - + + + - - IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0 + + Q*HCT*C_bc - - - - - + + + - + -(IsLiverZonated ? 0 : (Q_liv +Q_pve)*(1-HCT)*C_pls) - - - - - + + + + + - + IsLiverZonated ? 0 : (Q_liv +Q_pve)*(1-HCT)*C_pls - - - - - + + + + + - - -(IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0) + + -(Q*HCT*C_bc) - - - - - + + + - - IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0 + + Q*HCT*C_bc - - - - - + + + - - -(IsLiverZonated ? 0 : (Q_liv +Q_pve)*HCT*C_bc) + + -(Q*(1-HCT)*C_pls) - - - - - + + + - - IsLiverZonated ? 0 : (Q_liv +Q_pve)*HCT*C_bc + + Q*(1-HCT)*C_pls - - - - - + + + - + -(IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0) - - - - - + + + + + - + IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0 - - - - - + + + + + - - -(Q*(1-HCT)*C_pls) + + -(IsLiverZonated ? 0 : (Q_liv +Q_pve)*HCT*C_bc) - - - + + + + + - - Q*(1-HCT)*C_pls + + IsLiverZonated ? 0 : (Q_liv +Q_pve)*HCT*C_bc - - - + + + + + - - -(Q*HCT*C_bc) + + -(IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0) - - - + + + + + - - Q*HCT*C_bc + + IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0 - - - + + + + + - - -(Q*(1-HCT)*C_pls) + + -(IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0) - - - + + + + + - - Q*(1-HCT)*C_pls + + IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0 - - - + + + + + - - -(Q*HCT*C_bc) + + -(IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0) - - - + + + + + - - Q*HCT*C_bc + + IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0 - - - + + + + + - - P * P_pls_rbc_factor + + P_int_trans_default >0 ? P_int_trans / P_int_trans_default : 0 - - + + - - 10 ^ (m * log10 (P_int_InVitro) + b) + + (f_water_rbc + f_lipids_rbc * 10^LogMA + f_proteins_rbc * KProt)*fu - - - + + + + + + - - 10 ^ (m * log10 (P_int_InVitro) + b) + + P * P_rbc_pls_factor - - - + + - - P_int_trans_default >0 ? P_int_trans / P_int_trans_default : 0 + + 10 ^ (m * log10 (P_int_InVitro) + b) - - + + + - - P * P_rbc_pls_factor + + 10 ^ (m * log10 (P_int_InVitro) + b) - - + + + - - (f_water_rbc + f_lipids_rbc * 10^LogMA + f_proteins_rbc * KProt)*fu + + P * P_pls_rbc_factor - - - - - - + + - + 1 / (1 + (BindingPartner = Albumin ? AlbuminOntgenyFactor : (BindingPartner = Agp ? AgpOntogenyFactor : 1) ) * (1 - fu_ref) / fu_ref) * PlasmaProteinScaleFactor - - - - - - - + + + + + + + - + (f_water_rbc + f_lipids_rbc * 10^LogP + f_proteins_rbc * KProt) * fu * HCT - HCT + 1 - - - - - - - + + + + + + + - - CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Max(pKa_1;pKa_2) : (CT1 != CT_ACID ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 - - - - + + + + + + + - - CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + P_1 - - - - + - - CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Max(pKa_1;pKa_2) : (CT1 != CT_BASE ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 - - - - + + + + + + + - - F1*(1-F2)*(1-F3) + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - + + + + + + + + + + + + - - (1-F1)*F2*(1-F3) + + pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Min(pKa_1;pKa_2) : (CT1 != CT_ACID ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 - - - + + + + + + + - - (1-F1)*(1-F2)*F3 + + MW - F * 0.000000017 - Cl * 0.000000022 - Br * 0.000000062 - I * 0.000000098 - - - + + + + + - - F1*F2*(1-F3) + + pKa_Acids_Count=1 & pKa_Bases_Count = 0 ? 1 : 0 - - - + + - - F1*(1-F2)*F3 + + IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 - - - + + + - - (1-F1)*F2*F3 + + Br + Chlor + F + I > 0 - - - + + + + - - F1*F2*F3 + + pKa_Acids_Count=2 & pKa_Bases_Count = 0 ? 1 : 0 - - - + + - - (CT_0=1 AND pKa_0>=7) OR (CT_1=1 AND pKa_1>=7) OR (CT_2=1 AND pKa_2>=7) + + pKa_Acids_Count=0 & pKa_Bases_Count = 2 ? 1 : 0 - - - - - - + + - + pKa_Acids_Count=1 & pKa_Bases_Count = 2 ? 1 : 0 - - + + - - pKa_Acids_Count=1 & pKa_Bases_Count = 0 ? 1 : 0 + + pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Min(pKa_1;pKa_2) : (CT1 != CT_BASE ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 - - + + + + + + + - + pKa_Acids_Count=0 & pKa_Bases_Count = 1 ? 1 : 0 - - + + - - pKa_Acids_Count=2 & pKa_Bases_Count = 1 ? 1 : 0 + + F1*(1-F2)*F3 + + + + + + + + IsTriproticBase ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 - - + + + + - - pKa_Acids_Count=1 & pKa_Bases_Count = 1 ? 1 : 0 + + (CT0 = CT_BASE ? 1 : 0) + (CT1 = CT_BASE ? 1 : 0) + (CT2 = CT_BASE ? 1 : 0) - - + + + + - - pKa_TwoBases_1+pKa_ThreeBases_1 + + pKa_Acids_Count=1 ? (CT0=CT_ACID ? pKa_0 : (CT1=CT_ACID ? pKa_1 : pKa_2)) : 0 - - + + + + + + + - - CT_0 = 0 AND CT_1 = 0 AND CT_2 = 0 + + pKa_Bases_Count=1 ? (CT0=CT_BASE ? pKa_0 : (CT1=CT_BASE ? pKa_1 : pKa_2)) : 0 - - - + + + + + + + - - (CT0 = CT_ACID ? 1 : 0) + (CT1 = CT_ACID ? 1 : 0) + (CT2 = CT_ACID ? 1 : 0) + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 - - - - + + + + - - IsTriproticBase ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 - - - - + + + + - - pKa_Acids_Count=3 & pKa_Bases_Count = 0 ? 1 : 0 + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 - - + + + + - - pKa_Acids_Count=0 & pKa_Bases_Count = 3 ? 1 : 0 + + pKa_OneBase_0+pKa_TwoBases_0+pKa_ThreeBases_0 - - + + + - - pKa_OneAcid_0+pKa_TwoAcids_0+pKa_ThreeAcids_0 + + (1-F1)*F2*F3 - - - + + + - - pKa_TwoAcids_1+pKa_ThreeAcids_1 + + (CT0 = CT_ACID ? 1 : 0) + (CT1 = CT_ACID ? 1 : 0) + (CT2 = CT_ACID ? 1 : 0) - - + + + + - - IsTriproticAcid ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 + + F1*F2*(1-F3) - - - - + + + - - pKa_OneBase_0+pKa_TwoBases_0+pKa_ThreeBases_0 + + (1-F1)*(1-F2)*F3 - - - + + + - - (CT0 = CT_BASE ? 1 : 0) + (CT1 = CT_BASE ? 1 : 0) + (CT2 = CT_BASE ? 1 : 0) + + (1-F1)*F2*(1-F3) - - - - + + + - - pKa_Bases_Count=1 ? (CT0=CT_BASE ? pKa_0 : (CT1=CT_BASE ? pKa_1 : pKa_2)) : 0 + + F1*(1-F2)*(1-F3) - - - - - - - + + + - - pKa_Acids_Count=1 ? (CT0=CT_ACID ? pKa_0 : (CT1=CT_ACID ? pKa_1 : pKa_2)) : 0 + + (1-F1)*(1-F2)*(1-F3) - - - - - - - + + + - - IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 + + IsTriproticAcid ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 - - - + + + + - - pKa_Acids_Count=0 & pKa_Bases_Count = 2 ? 1 : 0 + + IsTriproticAcid ? (pKa_0 <= pKa_Acid_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Acid_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 - - + + + + + + - - pKa_Acids_Count=2 & pKa_Bases_Count = 0 ? 1 : 0 + + IsTriproticBase ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 - - + + + + - - MW - F * 0.000000017 - Cl * 0.000000022 - Br * 0.000000062 - I * 0.000000098 + + IsTriproticBase ? (pKa_0 <= pKa_Base_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Base_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 - - - - - + + + + + + - - Br + Chlor + F + I > 0 + + F1*F2*F3 - - - - + + + - - (1-F1)*(1-F2)*(1-F3) + + pKa_Acids_Count=2 & pKa_Bases_Count = 1 ? 1 : 0 - - - + + - - IsTriproticAcid ? (pKa_0 <= pKa_Acid_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Acid_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 + + pKa_Acids_Count=1 & pKa_Bases_Count = 1 ? 1 : 0 - - - - - - + + - - IsTriproticBase ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 + + CT_0 = 0 AND CT_1 = 0 AND CT_2 = 0 - - - - + + + - - IsTriproticBase ? (pKa_0 <= pKa_Base_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Base_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 + + (CT_0=1 AND pKa_0>=7) OR (CT_1=1 AND pKa_1>=7) OR (CT_2=1 AND pKa_2>=7) - - - - - - + + + + + + - - pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Min(pKa_1;pKa_2) : (CT1 != CT_ACID ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 + + pKa_Acids_Count=3 & pKa_Bases_Count = 0 ? 1 : 0 - - - - - - - + + - - pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Max(pKa_1;pKa_2) : (CT1 != CT_ACID ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 + + pKa_Acids_Count=0 & pKa_Bases_Count = 3 ? 1 : 0 - - - - - - - + + - - pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Min(pKa_1;pKa_2) : (CT1 != CT_BASE ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 + + pKa_TwoBases_1+pKa_ThreeBases_1 - - - - - - - + + - - pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Max(pKa_1;pKa_2) : (CT1 != CT_BASE ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 + + pKa_OneAcid_0+pKa_TwoAcids_0+pKa_ThreeAcids_0 - - - - - - - + + + - - K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) - - - - - - - - - - - - - - - - - P_1 + + pKa_TwoAcids_1+pKa_ThreeAcids_1 - + + - - IsTriproticAcid ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 + + IsTriproticAcid ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 - - - - + + + + - + IsSmallMolecule ? (MWEff *1E9 / 336) ^ (-6) * 10^LogMA / 5 * 1E-4 *1E-1: 0 - - - + + + - + IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 - - - + + + - + (0.81 + 0.11 * 10^LogMA) / 24.92 * 5.0 - + - + 60 * 10^(-4.113-0.4609*Log10(MW * 1E9)) *1E-2 - + - + 0,0333 * (MW * 1E9) ^ 0,4226 * 1E-8 - + - + Time=StartTime - + - + M + DrugMass - - + + - + Dose / MW - - + + - + DosePerBodyWeight * BW - - + + - + DrugMass - + - + V>0 ? M/V : 0 - - + + - + V>0 ? M/V : 0 - - + + - - 1E-09 + + 1E-10 - - 0.0001 + + 1E-05 - + 1E-10 - + 0 - + 60 - + 100000 - + 1 - + 1 - - - - - - - - - - - - + + + + + + + + + + + + - + 1 - - - - - - - - - - - - + + + + + + + + + + + + - + 1 - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + - + 1 - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - - - - + + + + + + - + 1 - - - + + + - + 1 - - + + - + 1 - + - + 1 - + + - + 1 - + - + 1 - + - + 1 - - - - - + - + 1 - + + + + + - + 1 - + - + 1 - - - - + - + 1 - + + + + - + 1 - + - + 1 - - - - + - + 1 - + + + + - + 1 - + - + 1 - - - - + - + 1 - + + + + - + 1 - + - + 1 - - - - + - + 1 - + + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - - - + - + 1 - + + + - + 1 - + - + 1 - + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + + - + 1 - - - - - - - - - + - + 1 - - - - - - - - + + + + + + + + + - + 1 - - + + + + + + + + - + 1 - + + - + 1 - - - - - + - + 1 - - - + + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - + + - + 1 - - - + + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - + + - + 1 - - - + + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - + + - + 1 - - - + + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - + + - + 1 - - - + + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - - - - - - + + - + 1 - - - - - - - - - + + + + + + + + + + - + 1 - - + + + + + + + + + - + 1 - + + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + - + 1 - - - - + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - - + + - + 1 - - - - - - + + - + 1 - - - - - + + + + + + - + 1 - - + + + + + - + 1 - + + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + + - + 1 - - - - + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + + - + 1 - - - - - - - - - - - - - - - - - - + - + 1 - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + - + 1 - - - - + + + + + + + + + + + + + + + + + + - + 1 - - - + + + + - + 1 - - + + + - + 1 - + + - + 1 - - - - + - + 1 - - - + + + + + + + + 1 + + + + - + 1 - - + + - + 1 - + - + 1 - + - + 1 - + -

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- - - - - - - - + + + + + + + + diff --git a/tests/models/pediatric_1-3years-Population.csv b/tests/models/pediatric_1-3years-Population.csv new file mode 100644 index 0000000..e2555d2 --- /dev/null +++ b/tests/models/pediatric_1-3years-Population.csv @@ -0,0 +1,1003 @@ +#Project: ModelTemplate +#PK-Sim version: 7.3.0.0 +"IndividualId","Gender","RaceIndex","Population Name","Organism|Weight [kg]","Organism|BMI [kg/dm²]","Organism|Gestational age [week(s)]","Organism|Age [year(s)]","Organism|Ontogeny factor (alpha1-acid glycoprotein)","Organism|Ontogeny factor (albumin)","Organism|Height [dm]","Organism|Hematocrit","Organism|VenousBlood|Volume [l]","Organism|ArterialBlood|Volume [l]","Organism|Bone|Specific blood flow rate [l/min/kg organ]","Organism|Bone|Volume [l]","Organism|Brain|Volume [l]","Organism|Brain|Specific blood flow rate [l/min/kg organ]","Organism|Fat|Volume [l]","Organism|Fat|Vf (neutral lipid)-PT","Organism|Fat|Vf (lipid)","Organism|Fat|Vf (phospholipid)-PT","Organism|Fat|Fraction interstitial","Organism|Fat|Vf (water)","Organism|Fat|Vf (water)-PT","Organism|Fat|Vf (neutral lipid)-RR","Organism|Fat|Vf (neutral lipid)-WS","Organism|Fat|Vf (neutral phospholipid)-RR","Organism|Fat|Vf (neutral phospholipid, plasma)-WS","Organism|Fat|Vf (extracellular water)-RR","Organism|Fat|Vf (intracellular water)-RR","Organism|Fat|Vf (water)-WS","Organism|Fat|Specific blood flow rate [l/min/kg organ]","Organism|Gonads|Volume [l]","Organism|Gonads|Specific blood flow rate [l/min/kg organ]","Organism|Heart|Volume [l]","Organism|Heart|Specific blood flow rate [l/min/kg organ]","Organism|Kidney|Volume [l]","Organism|Kidney|Maximal decreasing rate factor","Organism|Kidney|TM50 for GFR [week(s)]","Organism|Kidney|Age of aging onset [year(s)]","Organism|Kidney|GFRmat [l/min]","Organism|Kidney|Aging half-time [year(s)]","Organism|Kidney|Hill coefficient for GFR","Organism|Kidney|Hill coefficient for aging GFR","Organism|Kidney|Specific blood flow rate [l/min/kg organ]","Organism|Lumen|Effective surface area variability factor","Organism|Lumen|Stomach|Distal radius [dm]","Organism|Lumen|Stomach|GET_beta (Weibull function) variability factor","Organism|Lumen|Stomach|Gastric emptying time [min]","Organism|Lumen|Stomach|GET_alpha (Weibull function) variability factor","Organism|Lumen|Stomach|Length [dm]","Organism|Lumen|Stomach|Proximal radius [dm]","Organism|Lumen|Duodenum|Effective surface area enhancement factor","Organism|Lumen|UpperJejunum|Effective surface area enhancement factor","Organism|Lumen|LowerJejunum|Effective surface area enhancement factor","Organism|Lumen|UpperIleum|Effective surface area enhancement factor","Organism|Lumen|LowerIleum|Effective surface area enhancement factor","Organism|Lumen|Caecum|Effective surface area enhancement factor","Organism|Lumen|ColonAscendens|Effective surface area enhancement factor","Organism|Lumen|ColonTransversum|Effective surface area enhancement factor","Organism|Lumen|ColonDescendens|Effective surface area enhancement factor","Organism|Lumen|ColonSigmoid|Effective surface area enhancement factor","Organism|Lumen|Rectum|Effective surface area enhancement factor","Organism|Stomach|Volume [l]","Organism|Stomach|Specific blood flow rate [l/min/kg organ]","Organism|SmallIntestine|Small intestinal transit time [min]","Organism|SmallIntestine|Volume [l]","Organism|SmallIntestine|Specific blood flow rate [l/min/kg organ]","Organism|LargeIntestine|Large intestinal transit time [min]","Organism|LargeIntestine|Volume [l]","Organism|LargeIntestine|Specific blood flow rate [l/min/kg organ]","Organism|Liver|Volume [l]","Organism|Liver|Specific blood flow rate [l/min/kg organ]","Organism|Lung|Volume [l]","Organism|Lung|Fraction vascular","Organism|Muscle|Volume [l]","Organism|Muscle|Vf (neutral lipid)-PT","Organism|Muscle|Vf (lipid)","Organism|Muscle|Vf (protein)","Organism|Muscle|Vf (phospholipid)-PT","Organism|Muscle|Vf (water)-PT","Organism|Muscle|Vf (water)","Organism|Muscle|Fraction interstitial","Organism|Muscle|Vf (neutral lipid)-WS","Organism|Muscle|Vf (neutral lipid)-RR","Organism|Muscle|Vf (neutral phospholipid, plasma)-WS","Organism|Muscle|Vf (neutral phospholipid)-RR","Organism|Muscle|Vf (extracellular water)-RR","Organism|Muscle|Vf (protein)-WS","Organism|Muscle|Vf (intracellular water)-RR","Organism|Muscle|Vf (water)-WS","Organism|Muscle|Specific blood flow rate [l/min/kg organ]","Organism|Pancreas|Volume [l]","Organism|Pancreas|Specific blood flow rate [l/min/kg organ]","Organism|PortalVein|Volume [l]","Organism|Skin|Volume [l]","Organism|Skin|Specific blood flow rate [l/min/kg organ]","Organism|Spleen|Volume [l]","Organism|Spleen|Specific blood flow rate [l/min/kg organ]","CYP3A4|Reference concentration [µmol/l]","CYP3A4|t1/2 (liver) [min]","CYP3A4|t1/2 (intestine) [min]","CYP3A4|Ontogeny factor","CYP3A4|Ontogeny factor GI" +0,1,0,pediatric_1-3years,12.0872183661891,0.13944246317359,40,2.04729410682213,1.77510451623991,0.915296128321654,9.31034257477668,0.364729410682213,0.161260866327985,0.0707393156423272,0.0480000262987169,2.15290869548276,1.09390089726738,0.942381273178989,2.38682481509337,0.5925,0.6,0.0015,0.35,0.349999999995,0.419999999994,0.63975,0.69,0.0012,0.001518,0.3149999999955,0.0209999999997,0.069999999999,0.0193144214638328,0.00177855298873833,0.471635599165331,0.127679413070013,0.866466300670451,0.163971067394056,0.9,45.4666461722842,30,0.103073120284765,54,14.8417536131757,1.5,2.72119139722612,1.25312594321248,0.240455955628644,1.25029458049352,9.46071073906563,0.830682515732489,0.961813349573507,0.240455955628644,266.346353,407.668807,339.371578,237.284957,133.37415,1.638,2.275,2.275,2.275,2.275,3.2396,0.0264255661330163,0.535375343286791,71.3000745834511,0.12010810151626,1.33388215720262,2395.74988195242,0.105640778580698,0.863534635652108,0.660547512564062,0.213891100857715,0.27295890748929,0.58,3.93554870710204,0.0238,0.013,0.232836425544069,0.0072,0.766926099955824,0.818390877716017,0.309527058931779,0.0049,0.022,0.0042,0.0078,0.079719949863829,0.24993740595126,0.672069450750761,0.766926099955824,0.0317241043515804,0.00954245064803062,0.486112297398631,0.17189184022996,0.572675977970068,0.178009176815578,0.0528149006890047,0.867487224139518,4.32,2220,1380,0.813965603315142,1.59011939263424 +1,1,0,pediatric_1-3years,10.5200267109542,0.147600028318594,40,2.01008098805793,0.945659066063192,1.15448275458866,8.44238592052135,0.361008098805793,0.147945513359146,0.0593659610246151,0.0488447273404507,1.7462587440931,1.07451894563263,0.989609848706333,1.47453820636901,0.5925,0.6,0.0015,0.35,0.349999999995,0.419999999994,0.63975,0.69,0.0012,0.001518,0.3149999999955,0.0209999999997,0.069999999999,0.0192260372296141,0.00196282348839078,0.466828955103162,0.0801807641653984,0.809931315513877,0.142406028159932,0.9,43.7221806153659,30,0.137392818668302,54,14.655244301221,1.5,2.67132222120951,0.429584413693113,0.239583773157608,0.898852462578557,12.3233432865468,0.757761815678072,0.95832499182055,0.239583773157608,266.346353,407.668807,339.371578,237.284957,133.37415,1.638,2.275,2.275,2.275,2.275,3.2396,0.0371960384659013,0.547444647613895,144.233011793881,0.131726686048981,1.22070785747425,2394.37299655814,0.10573079105857,0.930087331158926,0.718973667594234,0.186118629524353,0.237278605618575,0.58,3.8172550580642,0.0238,0.013,0.233540135161725,0.0072,0.76701338998387,0.818484025364367,0.309899190119421,0.0049,0.022,0.0042,0.0078,0.0797290234325339,0.250692800456089,0.672145944380602,0.76701338998387,0.0277199913286864,0.0343612347618809,0.469763955977429,0.149441660879148,0.460588864287155,0.165707452846644,0.100297117883319,0.902364816432336,4.32,2220,1380,0.754117613729002,0.55968103823873 +2,1,0,pediatric_1-3years,11.1293480959303,0.138915748708124,40,2.42666262082134,1.06562613390537,1.1027904637434,8.95074369188013,0.37,0.142160947979912,0.0706036646906019,0.0532480889741832,1.9748745639919,1.1779107912107,0.902314883333952,2.74138816194069,0.5925,0.6,0.0015,0.35,0.349999999995,0.419999999994,0.63975,0.69,0.0012,0.001518,0.3149999999955,0.0209999999997,0.069999999999,0.0236054891174169,0.00192305355621939,0.489763453434573,0.0984643834464816,0.891880204718011,0.0591898593446234,0.9,44.1521769763024,30,0.0840043442208,54,14.9786809388181,1.5,2.70231136900512,0.485150909492548,0.2493474051755,1.54746947048947,17.7383345819216,0.678440029879674,0.997375354075793,0.2493474051755,266.346353,407.668807,339.371578,237.284957,133.37415,1.638,2.275,2.275,2.275,2.275,3.2396,0.0420346560750735,0.515374056390863,135.610489433149,0.130497260088086,1.28453222286878,2409.78651697039,0.0883532171399721,0.793364503308001,0.596749123607878,0.224840080818617,0.36185425165611,0.58,2.9055434967296,0.0238,0.013,0.225662469670366,0.0072,0.766036223231521,0.817441285579952,0.305733373791787,0.0049,0.022,0.0042,0.0078,0.0796274495201186,0.242236549363669,0.67128963772657,0.766036223231521,0.032314705012049,0.0376418821216186,0.544331938355154,0.164723995922171,0.48879900196538,0.189413578322293,0.0466357844632873,0.916997968567384,4.32,2220,1380,0.779191590706219,0.751457079040459 +3,1,0,pediatric_1-3years,12.2641188955023,0.195140357790694,40,1.54651534955321,0.83719903268029,1.11001765717448,7.92765291158865,0.36,0.119350513141405,0.0498031744371115,0.0480337737839353,1.528486691232,1.03084734359527,0.850585308964987,4.73555956671055,0.5925,0.6,0.0015,0.35,0.349999999995,0.419999999994,0.63975,0.69,0.0012,0.001518,0.3149999999955,0.0209999999997,0.069999999999,0.0188217746685612,0.00184921644152255,0.40940047859835,0.0428083703733492,0.821533805784989,0.0976229134218065,0.9,44.3001968311517,30,0.104056957083027,54,15.0818131353621,1.5,2.50646557366012,1.66845830240944,0.228718953505153,1.21878738522313,7.29698546227229,2.28507166045797,0.914870348867118,0.228718953505153,266.346353,407.668807,339.371578,237.284957,133.37415,1.638,2.275,2.275,2.275,2.275,3.2396,0.0290742003127409,0.493287733483293,66.3872475548691,0.129847281971678,1.24880472129447,2377.22106793347,0.0566980868508535,0.898628407499782,0.591445067715617,0.183487112988457,0.164572727021302,0.58,3.02665438227567,0.0238,0.013,0.242306280248834,0.0072,0.768100766127829,0.819644370170618,0.314534846504468,0.0049,0.022,0.0042,0.0078,0.0798420533211822,0.260102786707787,0.67309882926465,0.768100766127829,0.0338918317703607,0.0315036606701834,0.481767320997348,0.127626674606675,0.44976851166965,0.163329231945346,0.0506005130549034,0.761024580620805,4.32,2220,1380,0.797446400732989,0.489111045669474 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M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + F1*F2*F3 + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + +

+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + LuminalVelocity/SITT_fact + + + + + + + L_p0 + Height*L_p1 + + + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_sto - LT_duo + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + + + + + + + + + + + w*Liquid*FillLevelFlagNext + + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + 0.02894*V + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + V_Intestine * 0.087 + + + + + + Volume + + + + + + PI*(r1+r2)*L + + + + + + + + Liquid/V + + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + LuminalVelocity/SITT_fact + + + + + + + V_Intestine * 0.249 + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_duo - LT_uje + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + + + + + + + + + + + w*Liquid*FillLevelFlagNext + + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + 0.0031572*V + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + Volume + + + + + + PI*(r1+r2)*L + + + + + + + + L_p0 + Height*L_p1 + + + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + Liquid/V + + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + F1*(1-F2)*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*F2*F3 + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + +
+ + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + 0.0025102*V + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + V_Intestine * 0.184 + + + + + + L_p0 + Height*L_p1 + + + + + + + + Volume + + + + + + w*Liquid*FillLevelFlagNext + + + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_uje - LT_lje + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + + + + + + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + Liquid/V + + + + + + + PI*(r1+r2)*L + + + + + + + + LuminalVelocity/SITT_fact + + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + Liquid/V + + + + + + + PI*(r1+r2)*L + + + + + + + + LuminalVelocity/SITT_fact + + + + + + + L_p0 + Height*L_p1 + + + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_lje - LT_uil + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + + + + + + + + + + + 0.0029585*V + + + + + + w*Liquid*FillLevelFlagNext + + + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + V_Intestine * 0.324 + + + + + + Volume + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + tHalf + + + + + + f_onto + + + + + + V>0 ? M/V : 0 + + + + + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + +
+ + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + F1*(1-F2)*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*F2*F3 + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + V_Intestine * 0.156 + + + + + + Volume + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + Liquid/V + + + + + + + PI*(r1+r2)*L + + + + + + + + LuminalVelocity/SITT_fact + + + + + + + L_p0 + Height*L_p1 + + + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_uil - LT_lil + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + + + + + + + + + + + w*Liquid*FillLevelFlagNext + + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + 0.0017657*V + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + +
+ + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume + + + + + + V_Intestine * 0.08470588 + + + + + + LuminalVelocity/LITT_fact + + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + PI*(r1+r2)*L + + + + + + + + L_p0 + Height*L_p1 + + + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_lil - LT_cae + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + + + + + + + + + + + w*Liquid*FillLevelFlagNext + + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + 0*V + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + Liquid/V + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume + + + + + + V_Intestine * 0.15529412 + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_cae - LT_colasc + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + + + + + + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + Liquid/V + + + + + + + PI*(r1+r2)*L + + + + + + + + L_p0 + Height*L_p1 + + + + + + + + w*Liquid*FillLevelFlagNext + + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + 0.00098426*V + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + LuminalVelocity/LITT_fact + + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + tHalf + + + + + + f_onto + + + + + + V>0 ? M/V : 0 + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + F1*F2*(1-F3) + + + + + + + + F1*(1-F2)*F3 + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + Liquid/V + + + + + + + PI*(r1+r2)*L + + + + + + + + LuminalVelocity/LITT_fact + + + + + + + L_p0 + Height*L_p1 + + + + + + + + w*Liquid*FillLevelFlagNext + + + + + + + + 0.00020285*V + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + V_Intestine * 0.32 + + + + + + Volume + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_colasc - LT_coltrans + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + + + + + + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + tHalf + + + + + + f_onto + + + + + + V>0 ? M/V : 0 + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + F1*(1-F2)*F3 + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + Liquid/V + + + + + + + PI*(r1+r2)*L + + + + + + + + LuminalVelocity/LITT_fact + + + + + + + L_p0 + Height*L_p1 + + + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_coltrans - LT_coldesc + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + + + + + + + + + + + w*Liquid*FillLevelFlagNext + + + + + + + + 0.00023004*V + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + V_Intestine * 0.24 + + + + + + Volume + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + +
+ + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + PI*(r1+r2)*L + + + + + + + + LuminalVelocity/LITT_fact + + + + + + + L_p0 + Height*L_p1 + + + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_coldesc - LT_colsigm + Inflow*FillLevelFlag - Outflow*Liquid : 0 + + + + + + + + + + + + w*Liquid*FillLevelFlagNext + + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + 0.00013099*V + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + V_Intestine * 0.135 + + + + + + Volume + + + + + + Liquid/V + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + tHalf + + + + + + f_onto + + + + + + V>0 ? M/V : 0 + + + + + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + (k_p*alpha_p*V_p+inflow-k*alpha*V)/(alpha*V) + + + + + + + + + + + + r2_p0 + Height*r2_p1 + + + + + + + + Ageom*AeffFactor*AeffVariabilityFactor + + + + + + + + (FillLevel<0.9?1:1/(1+exp((FillLevel-1)/0.01))) + + + + + + Liquid/V + + + + + + + L_p0 + Height*L_p1 + + + + + + + + PI*(r1+r2)*L + + + + + + + + V_Intestine * 0.055 + + + + + + V*SteadyStateFillLevel + + + + + + + OralApplicationsEnabled ? LT_colsigm - LT_rect + Inflow*FillLevelFlag : 0 + + + + + + + + + + w*Liquid + + + + + + + r1_p0 + Height*r1_p1 + + + + + + + + 0.00071247*V + + + + + + Thickness_p1 + Thickness_p2*(1-exp(Thickness_p3*Height)) + + + + + + + + + PI*(r1*r1+r1*r2+r2*r2)/3*L + + + + + + + + Volume + + + + + + LuminalVelocity/LITT_fact + + + + + + + 0 + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + tHalf + + + + + + f_onto + + + + + + V>0 ? M/V : 0 + + + + + + +
+ + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + PassiveRates_para+PassiveRates_trans-(ActiveRates_para+ActiveRates_trans) + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + Solubility * Solubility_pKa_REFpH_Factor / Solubility_pKa_pH_Factor + SolubilityTable + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + min(Solubility/MW ; M/Liquid) + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + OralApplicationsEnabled ? LT_rec : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + TotalOralDrugMass > 0 ? (M_sto + M_duo + M_uje + M_lje + M_uil + M_lil + M_cae + M_colasc + M_coltrans + M_coldesc + M_colsigm + M_rect + M_fec + Mabs_Mucosa) / TotalOralDrugMass : 0 + + + + + + + + + + + + + + + + + + + + OralDrugMass>0.0 ? MassAbsorbed/OralDrugMass : 0 + + + + + + + Volume * Density + + + + + + + SA_pls_int*d_endo + + + + + + + f_lymph*Q*(1-HCT) + + + + + + + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) + + + + + + + + + + + 1 - f_int - f_vas + + + + + + + Qspec * Weight + + + + + + + Volume + + + + + + f_vas*(1-HCT)*V_org + + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_pls_norm + + + + + + rel_exp_norm + + + + + + rel_exp_pls + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + fu + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume + + + + + + f_vas*HCT*V + + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_bc_norm + + + + + + rel_exp_norm + + + + + + rel_exp_bc + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + K_rbc/fu + + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume + + + + + + f_int*V + + + + + + + pH_int + + + + + + V>0 ? M/V : 0 + + + + + + + K_water_int + + + + + + V>0 ? M/V : 0 + + + + + + + Volume + + + + + + f_cell*V + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + K_water_cell + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + C_int * K_water_int + + + + + + + C_cell * K_water_cell + + + + + + + (f_int*C_int+f_cell*C_cell)/(f_int+f_cell) + + + + + + + + + Volume * Density + + + + + + + P1*SITT+P2 + + + + + + + + J_iso_incl_Mucosa-J_iso_duo-J_iso_uje-J_iso_lje-J_iso_uil-J_iso_lil + + + + + + + + + + + SA_pls_int*d_endo + + + + + + + f_Jiso * (1-alpha_l) * Q_lymph * (V/V_mouse)^(exp_Jiso_scale - 1) + + + + + + + + + + + Q_lymph_incl_Mucosa-Q_lymph_duo-Q_lymph_uje-Q_lymph_lje-Q_lymph_uil-Q_lymph_lil + + + + + + + + + + + f_lymph*Q*(1-HCT) + + + + + + + + 1 - f_int - f_vas + + + + + + + Qspec * Weight + + + + + + + V_duo+V_uje+V_lje+V_uil+V_lil + + + + + + + + + + 0 + + + 126.000000328837 + + + Volume + + + + + + f_vas*(1-HCT)*(V-V_Mucosa) + + + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_pls_norm + + + + + + rel_exp_norm + + + + + + rel_exp_pls + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + fu + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume + + + + + + f_vas*HCT*(V-V_Mucosa) + + + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_bc_norm + + + + + + rel_exp_norm + + + + + + rel_exp_bc + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + K_rbc/fu + + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume + + + + + + f_int*(V-V_Mucosa) + + + + + + + + pH_int + + + + + + V>0 ? M/V : 0 + + + + + + + K_water_int + + + + + + V>0 ? M/V : 0 + + + + + + + Volume-V_Mucosa + + + + + + + f_cell*(V-V_Mucosa) + + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + tHalf + + + + + + f_onto + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + K_water_cell + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume * Density + + + + + + + V_GutWall*fractionMucosa + + + + + + + Q_lymph_intestine * V_seg / V_intestine + + + + + + + + SA_pls_int*d_endo + + + + + + + J_iso_intestine * V_seg / V_intestine + + + + + + + + Q * fractQ * regionalFractQ + + + + + + + + 1 - f_int - f_vas + + + + + + + 0 + + + Volume + + + + + + f_vas*(1-HCT)*V_org + + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_pls_norm + + + + + + rel_exp_norm + + + + + + rel_exp_pls + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + fu + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume + + + + + + f_vas*HCT*V + + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_bc_norm + + + + + + rel_exp_norm + + + + + + rel_exp_bc + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + tHalf + + + + + + f_onto + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + K_rbc/fu + + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume + + + + + + f_int*V + + + + + + + pH_int + + + + + + V>0 ? M/V : 0 + + + + + + + K_water_int + + + + + + V>0 ? M/V : 0 + + + + + + + Volume + + + + + + f_cell*V + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_norm + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + tHalf + + + + + + f_onto + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + K_water_cell + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume * Density + + + + + + + V_GutWall*fractionMucosa + + + + + + + J_iso_intestine * V_seg / V_intestine + + + + + + + + SA_pls_int*d_endo + + + + + + + Q_lymph_intestine * V_seg / V_intestine + + + + + + + + Q * fractQ * regionalFractQ + + + + + + + + 1 - f_int - f_vas + + + + + + + 0 + + + Volume + + + + + + f_vas*(1-HCT)*V_org + + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_pls_norm + + + + + + rel_exp_norm + + + + + + rel_exp_pls + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + fu + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? M/TotalDrugMass : 0 + + + + + + + -(CP * kcat * V * K_water * C / (Km + K_water * C)) + + + + + + + + + + + CP * kcat * V * K_water * C / (Km + K_water * C) + + + + + + + + + + + Km * Km_interaction_factor + + + + + + + kcat * kcat_interaction_factor + + + + + + + Volume + + + + + + f_vas*HCT*V + + + + + + + + M_0 + + + + + + rel_exp_out * AF * f_onto * ProteinContainerVolume + + + + + + + + + rel_exp_bc_norm + + + + + + rel_exp_norm + + + + + + rel_exp_bc + + + + + + ln(2)/tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + f_onto + + + + + + tHalf + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + K_rbc/fu + + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + TotalDrugMass>0 ? 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PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + P * P_int_cell_factor + + + + + + + P * P_cell_int_factor + + + + + + + P_int_cell * SA + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + (V_hrt * 1000 / 1.2)^0.75 * 7.54 * 1E2 + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + K_water_cell + + + + + + fu/K_cell_pls + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + P * P_int_cell_factor + + + + + + + P * P_cell_int_factor + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + (V_kid * 1000 / 7)^0.75 * 1000 * 1E2 + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + P_1 + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + 0 + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + P_1 + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + K_water_cell + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + -(fu * GFRspec*GFR_Fraction* Weight_Kidney * C_kid_pls) + + + + + + + + + + fu * GFRspec*GFR_Fraction* Weight_Kidney * C_kid_pls + + + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + 0 + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*F2*F3 + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + + + + + K_water_cell + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + P_1 + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + 0 + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + P_1 + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + -(OralApplicationsEnabled ? w*Drug : 0) + + + + + + + + OralApplicationsEnabled ? w*Drug : 0 + + + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + MAbs_duo + MAbs_uje + MAbs_lje + MAbs_uil + MAbs_lil + MAbs_cae + MAbs_colasc + MAbs_coltrans + MAbs_coldesc + MAbs_colsigm + MAbs_rect + + + + + + + + + + + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + -((OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0) + + + + + + + + + + (OralApplicationsEnabled AND IsFloatingInLumen) ? w*Drug*FillLevelFlagNext : 0 + + + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + F1*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + 0 + + + P_1 + + + + + + F1*(1-F2)*F3 + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + F1*F2*(1-F3) + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + + + + + K_water_cell + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + P_cell_int * SA + + + + + + + P * P_int_cell_factor + + + + + + + P * P_cell_int_factor + + + + + + + P_int_cell * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + (V_sto * 1000 / 1.1)^0.75 * 1000 * 1E2 + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + P_1 + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + -((1-fractQ)*Q*HCT*C) + + + + + + + + + (1-fractQ)*Q*HCT*C + + + + + + + + + P * P_int_cell_factor + + + + + + + P * P_cell_int_factor + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + ((V_sin-V_Mucosa) * 1000 / 11.1)^0.75 * 1000 * 1E2 + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * (V_org-V_Mucosa) + + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * (V-V_Mucosa) * f_vas + + + + + + + + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + P_1 + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + 0 + + + P_1 + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + + + + + K_water_cell + + + + + + (1-F1)*F2*F3 + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + -((1-fractQ)*Q*(1-HCT)*C) + + + + + + + + + (1-fractQ)*Q*(1-HCT)*C + + + + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferIntestineToMucosaPlasmaRate) + + + + + + MassTransferIntestineToMucosaPlasmaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferIntestineToMucosaBCRate) + + + + + + MassTransferIntestineToMucosaBCRate + + + + + + -((1-fractQ)*Q*HCT*C) + + + + + + + + + (1-fractQ)*Q*HCT*C + + + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + P * P_int_cell_factor + + + + + + + P * P_cell_int_factor + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + fu/K_cell_pls + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + ((V_lin-V_Mucosa) * 1000 / 11.1)^0.75 * 1000 * 1E2 + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * (V-V_Mucosa) * f_vas + + + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * (V_org-V_Mucosa) + + + + + + + + + -((1-fractQ)*Q*(1-HCT)*C) + + + + + + + + + (1-fractQ)*Q*(1-HCT)*C + + + + + + + + + (V_liv * 1000 / 10)^0.75 * 82 * 1E2 + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(EHC_Active ? ln(2) / EHC_Halftime * M * EHC_EjectionFraction : 0) + + + + + + + + + EHC_Active ? ln(2) / EHC_Halftime * M * EHC_EjectionFraction : 0 + + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + SA_pls_bc * (IsLiverZonated? f_periportal : 1) + + + + + + + + fu/K_cell_pls + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + P_cell_int * SA + + + + + + + P_int_cell * SA + + + + + + + P * P_cell_int_factor + + + + + + + P * P_int_cell_factor + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + SA_int_cell * (IsLiverZonated? f_periportal : 1) + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + SA_pls_int * (IsLiverZonated? f_periportal : 1) + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + SA_pls_int * (IsLiverZonated? 1-f_periportal : 0) + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + SA_pls_bc * (IsLiverZonated? 1-f_periportal : 0) + + + + + + + + P * P_int_cell_factor + + + + + + + P_cell_int * SA + + + + + + + P * P_cell_int_factor + + + + + + + P_int_cell * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + SA_int_cell * (IsLiverZonated? 1-f_periportal : 0) + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + P * P_int_cell_factor + + + + + + + P * P_cell_int_factor + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + (V_lng * 1000 / 2.2)^0.75 * 0.096 * 1E2 + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + P_int_cell * SA + + + + + + + P * P_cell_int_factor + + + + + + + P_cell_int * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + P * P_int_cell_factor + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + (V_mus * 1000 / 110.1)^0.75 * 7.54 * 1E2 + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + P * P_int_cell_factor + + + + + + + P * P_cell_int_factor + + + + + + + P_int_cell * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + P_cell_int * SA + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + (V_pan * 1000 / 1.3)^0.75 * 1000 * 1E2 + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + K_water_cell + + + + + + (1-F1)*F2*F3 + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + 0 + + + P_1 + + + + + + F1*F2*F3 + + + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + 0 + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V + + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + P * P_int_cell_factor + + + + + + + P * P_cell_int_factor + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + fu/K_cell_pls + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + (V_skn * 1000 / 43.4)^0.75 * 0.12 * 1E2 + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + P_cell_int * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + P * P_cell_int_factor + + + + + + + P * P_int_cell_factor + + + + + + + P_int_cell * SA + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + (V_spl * 1000 / 1.3)^0.75 * 1000 * 1E2 + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + R * fu + + + + + + + 1 + + + + + + + + + + -(fu * (C_pls_art - C_slv / K_slv_pls) * Q_slv) + + + + + + + + + + fu * (C_pls_art - C_slv / K_slv_pls) * Q_slv + + + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + fu/K_cell_pls + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + P_cell_int * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + P_int_cell * SA + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + fu/K_cell_pls + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + fu/K_cell_pls + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + P_cell_int * SA + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P_int_cell * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + P_cell_int * SA + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + P_int_cell * SA + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + fu/K_cell_pls + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + (f_water_int + f_proteins_int_to_pls * (1/fu - f_water_pls)) * fu + + + + + + + + + -(fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)) + + + + + + + + + + + fu * P_endothelial * SA * (C_pls - C_int / K_int_pls) + + + + + + + + + + + k * f_vas_org * V_org + + + + + + + + fu/K_cell_pls + + + + + + + ((1+X)/(1+Y)*f_iw + f_ew + (10^LogP*f_nl+(0.3*10^LogP+0.7)*f_np)/(1+Y) + (HasStrongBase ? Ka_AP*AP_T*X/(1+Y) : Ka_PR*(IsNeutral ? PR_T2PR_P_Lipoprotein : PR_T2PR_P_Albumin)))*fu + + + + + + + + + + + + + + + + + + + + P * P_int_cell_factor * P_int_scalefactor + + + + + + + + P * P_cell_int_factor * P_int_scalefactor + + + + + + + + P_int_cell * SA + + + + + + + P_cell_int * SA + + + + + + + fu/K_int_pls + + + + + + + -(K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell) + + + + + + + + + + + K_water_int * PA_int_cell * C_int - K_water_cell * PA_cell_int * C_cell + + + + + + + + + + + Aeff / MicrovilliFactor + + + + + + + -(SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc)) + + + + + + + + + + + + SA_bc * fu * (P_pls_rbc * C_pls - P_rbc_pls * C_bc /K_rbc) + + + + + + + + + + + + HCT * A_to_V_bc * 0.6 * V * f_vas + + + + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + 0 + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + 0 + + + P_1 + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + + + + + K_water_cell + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + 0 + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + + + + + K_water_cell + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + 0 + + + P_1 + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + 0 + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + 0 + + + P_1 + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + (1-F1)*F2*F3 + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + + + + + K_water_cell + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + 0 + + + P_1 + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + + + + + K_water_cell + + + + + + (1-F1)*F2*F3 + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + K_cell_pls + + + + + + K_water_cell + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + 0 + + + P_1 + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + 0 + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + 0 + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + OralApplicationsEnabled ? P_int_para*Aeff*(min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_para ? fu*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + 0 + + + P_1 + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + K_water_cell + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + F1*F2*F3 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + F1*(1-F2)*F3 + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + K_cell_pls + + + + + + UsePenaltyFactor ? K1+ (K2 +K3 +K4)* base ^ 1 + K5* base ^ max(CT0+CT1;-CT0-CT1) +K6* base ^ max(CT0+CT2;-CT0-CT2) +K7* base ^ max(CT2+CT1;-CT2-CT1) +K8* base ^ max(CT0+CT1+CT2;-CT0-CT1-CT2) : 1 + + + + + + + + + + + + + + + + + + OralApplicationsEnabled ? P_int_trans*Aeff*(P_int_trans_lum_cell_factor*min(Solubility/ MW ;DrugLiquid/(Liquid))-(NOT SinkCondition_trans ? P_int_trans_cell_lum_factor*fu/K_cell_pls*DrugMucosa : 0)) : 0 + + + + + + + + + + + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + 0 + + + P_1 + + + + + + -(DrugAbsorptionLumenToMucosaRate) + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + DrugAbsorptionLumenToMucosaRate + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(MassTransferMucosaToPvePlasmaRate) + + + + + + MassTransferMucosaToPvePlasmaRate + + + + + + Q*HCT*C_bc + + + + + + + + -(MassTransferMucosaToPveBCRate) + + + + + + MassTransferMucosaToPveBCRate + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(IsLiverZonated ? 0 : (Q_liv +Q_pve)*HCT*C_bc) + + + + + + + + + + IsLiverZonated ? 0 : (Q_liv +Q_pve)*HCT*C_bc + + + + + + + + + + -(IsLiverZonated ? 0 : (Q_liv +Q_pve)*(1-HCT)*C_pls) + + + + + + + + + + IsLiverZonated ? 0 : (Q_liv +Q_pve)*(1-HCT)*C_pls + + + + + + + + + + -(IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0) + + + + + + + + + + IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0 + + + + + + + + + + -(IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0) + + + + + + + + + + IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0 + + + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*(1-HCT)*C_pls) + + + + + + + + Q*(1-HCT)*C_pls + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + -(IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0) + + + + + + + + + + IsLiverZonated ? (Q_liv +Q_pve)*HCT*C_bc : 0 + + + + + + + + + + -(IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0) + + + + + + + + + + IsLiverZonated ? (Q_liv +Q_pve)*(1-HCT)*C_pls : 0 + + + + + + + + + + -(Q*HCT*C_bc) + + + + + + + + Q*HCT*C_bc + + + + + + + + P_int_trans_default >0 ? P_int_trans / P_int_trans_default : 0 + + + + + + + K_pu_bc*fu + + + + + + + P * P_rbc_pls_factor + + + + + + + 10 ^ (m * log10 (P_int_InVitro) + b) + + + + + + + + 10 ^ (m * log10 (P_int_InVitro) + b) + + + + + + + + P * P_pls_rbc_factor + + + + + + + 1 / (1 + (BindingPartner = Albumin ? AlbuminOntgenyFactor : (BindingPartner = Agp ? AgpOntogenyFactor : 1) ) * (1 - fu_ref) / fu_ref) * PlasmaProteinScaleFactor + + + + + + + + + + + + (f_water_rbc + f_lipids_rbc * 10^LogP + f_proteins_rbc * KProt) * fu * HCT - HCT + 1 + + + + + + + + + + + + pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Max(pKa_1;pKa_2) : (CT1 != CT_ACID ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + P_1 + + + + + + pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Max(pKa_1;pKa_2) : (CT1 != CT_BASE ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Min(pKa_1;pKa_2) : (CT1 != CT_ACID ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + MW - F * 0.000000017 - Cl * 0.000000022 - Br * 0.000000062 - I * 0.000000098 + + + + + + + + + + pKa_Acids_Count=1 & pKa_Bases_Count = 0 ? 1 : 0 + + + + + + + IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 + + + + + + + + Br + Chlor + F + I > 0 + + + + + + + + + pKa_Acids_Count=2 & pKa_Bases_Count = 0 ? 1 : 0 + + + + + + + pKa_Acids_Count=0 & pKa_Bases_Count = 2 ? 1 : 0 + + + + + + + pKa_Acids_Count=1 & pKa_Bases_Count = 2 ? 1 : 0 + + + + + + + pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Min(pKa_1;pKa_2) : (CT1 != CT_BASE ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + pKa_Acids_Count=0 & pKa_Bases_Count = 1 ? 1 : 0 + + + + + + + F1*(1-F2)*F3 + + + + + + + + IsTriproticBase ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 + + + + + + + + + (CT0 = CT_BASE ? 1 : 0) + (CT1 = CT_BASE ? 1 : 0) + (CT2 = CT_BASE ? 1 : 0) + + + + + + + + + pKa_Acids_Count=1 ? (CT0=CT_ACID ? pKa_0 : (CT1=CT_ACID ? pKa_1 : pKa_2)) : 0 + + + + + + + + + + + + pKa_Bases_Count=1 ? (CT0=CT_BASE ? pKa_0 : (CT1=CT_BASE ? pKa_1 : pKa_2)) : 0 + + + + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + pKa_OneBase_0+pKa_TwoBases_0+pKa_ThreeBases_0 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + (CT0 = CT_ACID ? 1 : 0) + (CT1 = CT_ACID ? 1 : 0) + (CT2 = CT_ACID ? 1 : 0) + + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + IsTriproticAcid ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 + + + + + + + + + IsTriproticAcid ? (pKa_0 <= pKa_Acid_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Acid_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 + + + + + + + + + + + IsTriproticBase ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 + + + + + + + + + IsTriproticBase ? (pKa_0 <= pKa_Base_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Base_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 + + + + + + + + + + + F1*F2*F3 + + + + + + + + pKa_Acids_Count=2 & pKa_Bases_Count = 1 ? 1 : 0 + + + + + + + pKa_Acids_Count=1 & pKa_Bases_Count = 1 ? 1 : 0 + + + + + + + CT_0 = 0 AND CT_1 = 0 AND CT_2 = 0 + + + + + + + + (CT_0=1 AND pKa_0>=7) OR (CT_1=1 AND pKa_1>=7) OR (CT_2=1 AND pKa_2>=7) + + + + + + + + + + + pKa_Acids_Count=3 & pKa_Bases_Count = 0 ? 1 : 0 + + + + + + + pKa_Acids_Count=0 & pKa_Bases_Count = 3 ? 1 : 0 + + + + + + + pKa_TwoBases_1+pKa_ThreeBases_1 + + + + + + + pKa_OneAcid_0+pKa_TwoAcids_0+pKa_ThreeAcids_0 + + + + + + + + pKa_TwoAcids_1+pKa_ThreeAcids_1 + + + + + + + IsTriproticAcid ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 + + + + + + + + + IsSmallMolecule ? (MWEff *1E9 / 336) ^ (-6) * 10^LogMA / 5 * 1E-4 *1E-1: 0 + + + + + + + + (0.81 + 0.11 * 10^LogMA) / 24.92 * 5.0 + + + + + + 60 * 10^(-4.113-0.4609*Log10(MW * 1E9)) *1E-2 + + + + + + 0,0333 * (MW * 1E9) ^ 0,4226 * 1E-8 + + + + + + Max(0;Kpu_bc - (1+Z)/(1+Y)*f_iw_bc - (10^LogP*f_nl_bc + (0.3*10^LogP+0.7)*f_np_bc)/(1+Y)) * (1+Y) / AP_bc / Z + + + + + + + + + + + + + + Max(0;1/fu - 1 - (10^LogP*f_nl_p + (0.3*10^LogP+0.7)*f_np_p)/(1+Y)) + + + + + + + + + + + 1.115 * LogP - 1.35 + + + + + + (HCT - 1 + B2P) / fu / HCT + + + + + + + + X_Neutral + X_MonoproticBase + X_MonoproticAcid + X_DiproticBase + X_DiproticAcid + X_MonoproticBaseMonoproticAcid + X_TriproticAcid + X_TriproticBase + X_DiproticBaseMonoproticAcid + X_MonoproticBaseDiproticAcid + + + + + + + + + + + + + + + IsDiproticAcid ? 10^(pH_IW-pKa_Acid_0) + 10^(2*pH_IW-pKa_Acid_0-pKa_Acid_1) : 0 + + + + + + + + + IsDiproticBase ? 10^(pKa_Base_1-pH_IW) + 10^(pKa_Base_0+pKa_Base_1-2*pH_IW) : 0 + + + + + + + + + IsDiproticBaseMonoproticAcid ? 10^(pH_IW-pKa_Acid_0) + 10^(pKa_Base_1-pH_IW) + 10^(pKa_Base_0+pKa_Base_1-2*pH_IW) : 0 + + + + + + + + + + IsMonoproticAcid ? 10^(pH_IW-pKa_Acid_0) : 0 + + + + + + + + IsMonoproticBase ? 10^(pKa_Base_0-pH_IW) : 0 + + + + + + + + IsMonoproticBaseDiproticAcid ? 10^(pKa_Base_0-pH_IW) + 10^(pH_IW-pKa_Acid_0) + 10^(2*pH_IW-pKa_Acid_0-pKa_Acid_1) : 0 + + + + + + + + + + IsMonoproticBaseMonoproticAcid ? 10^(pKa_Base_0-pH_IW) + 10^(pH_IW-pKa_Acid_0) : 0 + + + + + + + + + IsTriproticAcid ? 10^(pH_IW-pKa_Acid_0) + 10^(2*pH_IW-pKa_Acid_0-pKa_Acid_1) + 10^(3*pH_IW-pKa_Acid_0-pKa_Acid_1-pKa_Acid_2) : 0 + + + + + + + + + + IsTriproticBase ? 10^(pKa_Base_2-pH_IW) + 10^(pKa_Base_2+pKa_Base_1-2*pH_IW) + 10^(pKa_Base_0+pKa_Base_1+pKa_Base_2-3*pH_IW) : 0 + + + + + + + + + + Y_Neutral + Y_MonoproticBase + Y_MonoproticAcid + Y_DiproticBase + Y_DiproticAcid + Y_MonoproticBaseMonoproticAcid + Y_TriproticAcid + Y_TriproticBase + Y_DiproticBaseMonoproticAcid + Y_MonoproticBaseDiproticAcid + + + + + + + + + + + + + + + IsDiproticAcid ? 10^(pH_PLS-pKa_Acid_0) + 10^(2*pH_PLS-pKa_Acid_0-pKa_Acid_1) : 0 + + + + + + + + + IsDiproticBase ? 10^(pKa_Base_1-pH_PLS) + 10^(pKa_Base_0+pKa_Base_1-2*pH_PLS) : 0 + + + + + + + + + IsDiproticBaseMonoproticAcid ? 10^(pH_PLS-pKa_Acid_0) + 10^(pKa_Base_1-pH_PLS) + 10^(pKa_Base_0+pKa_Base_1-2*pH_PLS) : 0 + + + + + + + + + + IsMonoproticAcid ? 10^(pH_PLS-pKa_Acid_0) : 0 + + + + + + + + IsMonoproticBase ? 10^(pKa_Base_0-pH_PLS) : 0 + + + + + + + + IsMonoproticBaseDiproticAcid ? 10^(pKa_Base_0-pH_PLS) + 10^(pH_PLS-pKa_Acid_0) + 10^(2*pH_PLS-pKa_Acid_0-pKa_Acid_1) : 0 + + + + + + + + + + IsMonoproticBaseMonoproticAcid ? 10^(pKa_Base_0-pH_PLS) + 10^(pH_PLS-pKa_Acid_0) : 0 + + + + + + + + + IsTriproticAcid ? 10^(pH_PLS-pKa_Acid_0) + 10^(2*pH_PLS-pKa_Acid_0-pKa_Acid_1) + 10^(3*pH_PLS-pKa_Acid_0-pKa_Acid_1-pKa_Acid_2) : 0 + + + + + + + + + + IsTriproticBase ? 10^(pKa_Base_2-pH_PLS) + 10^(pKa_Base_2+pKa_Base_1-2*pH_PLS) + 10^(pKa_Base_0+pKa_Base_1+pKa_Base_2-3*pH_PLS) : 0 + + + + + + + + + + Z_Neutral + Z_MonoproticBase + Z_MonoproticAcid + Z_DiproticBase + Z_DiproticAcid + Z_MonoproticBaseMonoproticAcid + Z_TriproticAcid + Z_TriproticBase + Z_DiproticBaseMonoproticAcid + Z_MonoproticBaseDiproticAcid + + + + + + + + + + + + + + + IsDiproticAcid ? 1 : 0 + + + + + + IsDiproticBase ? 10^(pKa_Base_1-pH_RBC) + 10^(pKa_Base_0+pKa_Base_1-2*pH_RBC) : 0 + + + + + + + + + IsDiproticBaseMonoproticAcid ? 10^(pH_RBC-pKa_Acid_0) + 10^(pKa_Base_1-pH_RBC) + 10^(pKa_Base_0+pKa_Base_1-2*pH_RBC) : 0 + + + + + + + + + + IsMonoproticAcid ? 1 : 0 + + + + + + IsMonoproticBase ? 10^(pKa_Base_0-pH_RBC) : 0 + + + + + + + + IsMonoproticBaseDiproticAcid ? 10^(pKa_Base_0-pH_RBC) + 10^(pH_RBC-pKa_Acid_0) + 10^(2*pH_RBC-pKa_Acid_0-pKa_Acid_1) : 0 + + + + + + + + + + IsMonoproticBaseMonoproticAcid ? 10^(pKa_Base_0-pH_RBC) + 10^(pH_RBC-pKa_Acid_0) : 0 + + + + + + + + + IsNeutral ? 1 : 0 + + + + + + IsTriproticAcid ? 1 : 0 + + + + + + IsTriproticBase ? 10^(pKa_Base_2-pH_RBC) + 10^(pKa_Base_2+pKa_Base_1-2*pH_RBC) + 10^(pKa_Base_0+pKa_Base_1+pKa_Base_2-3*pH_RBC) : 0 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Max(pKa_1;pKa_2) : (CT1 != CT_ACID ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + 0 + + + pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Max(pKa_1;pKa_2) : (CT1 != CT_BASE ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Min(pKa_1;pKa_2) : (CT1 != CT_ACID ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + MW - F * 0.000000017 - Cl * 0.000000022 - Br * 0.000000062 - I * 0.000000098 + + + + + + + + + + pKa_Acids_Count=1 & pKa_Bases_Count = 0 ? 1 : 0 + + + + + + + IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 + + + + + + + + Br + Chlor + F + I > 0 + + + + + + + + + pKa_Acids_Count=2 & pKa_Bases_Count = 0 ? 1 : 0 + + + + + + + pKa_Acids_Count=0 & pKa_Bases_Count = 2 ? 1 : 0 + + + + + + + pKa_Acids_Count=1 & pKa_Bases_Count = 2 ? 1 : 0 + + + + + + + pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Min(pKa_1;pKa_2) : (CT1 != CT_BASE ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + pKa_Acids_Count=0 & pKa_Bases_Count = 1 ? 1 : 0 + + + + + + + F1*(1-F2)*F3 + + + + + + + + IsTriproticBase ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 + + + + + + + + + (CT0 = CT_BASE ? 1 : 0) + (CT1 = CT_BASE ? 1 : 0) + (CT2 = CT_BASE ? 1 : 0) + + + + + + + + + pKa_Acids_Count=1 ? (CT0=CT_ACID ? pKa_0 : (CT1=CT_ACID ? pKa_1 : pKa_2)) : 0 + + + + + + + + + + + + pKa_Bases_Count=1 ? (CT0=CT_BASE ? pKa_0 : (CT1=CT_BASE ? pKa_1 : pKa_2)) : 0 + + + + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + pKa_OneBase_0+pKa_TwoBases_0+pKa_ThreeBases_0 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + (CT0 = CT_ACID ? 1 : 0) + (CT1 = CT_ACID ? 1 : 0) + (CT2 = CT_ACID ? 1 : 0) + + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + IsTriproticAcid ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 + + + + + + + + + IsTriproticAcid ? (pKa_0 <= pKa_Acid_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Acid_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 + + + + + + + + + + + IsTriproticBase ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 + + + + + + + + + IsTriproticBase ? (pKa_0 <= pKa_Base_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Base_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 + + + + + + + + + + + F1*F2*F3 + + + + + + + + pKa_Acids_Count=2 & pKa_Bases_Count = 1 ? 1 : 0 + + + + + + + pKa_Acids_Count=1 & pKa_Bases_Count = 1 ? 1 : 0 + + + + + + + CT_0 = 0 AND CT_1 = 0 AND CT_2 = 0 + + + + + + + + (CT_0=1 AND pKa_0>=7) OR (CT_1=1 AND pKa_1>=7) OR (CT_2=1 AND pKa_2>=7) + + + + + + + + + + + pKa_Acids_Count=3 & pKa_Bases_Count = 0 ? 1 : 0 + + + + + + + pKa_Acids_Count=0 & pKa_Bases_Count = 3 ? 1 : 0 + + + + + + + pKa_TwoBases_1+pKa_ThreeBases_1 + + + + + + + pKa_OneAcid_0+pKa_TwoAcids_0+pKa_ThreeAcids_0 + + + + + + + + pKa_TwoAcids_1+pKa_ThreeAcids_1 + + + + + + + IsTriproticAcid ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 + + + + + + + + + IsSmallMolecule ? (MWEff *1E9 / 336) ^ (-6) * 10^LogMA / 5 * 1E-4 *1E-1: 0 + + + + + + + + IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 + + + + + + + + (0.81 + 0.11 * 10^LogMA) / 24.92 * 5.0 + + + + + + 60 * 10^(-4.113-0.4609*Log10(MW * 1E9)) *1E-2 + + + + + + 0,0333 * (MW * 1E9) ^ 0,4226 * 1E-8 + + + + + + pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Max(pKa_1;pKa_2) : (CT1 != CT_ACID ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + 0 + + + pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Max(pKa_1;pKa_2) : (CT1 != CT_BASE ? Max(pKa_0;pKa_2) : Max(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + K1+K2/base^(CT0^2)+K3/base^(CT1^2)+K4/base^(CT2^2)+K5/base^max(CT0+CT1;-CT0-CT1)+K6/base^max(CT0+CT2;-CT0-CT2)+K7/base^max(CT1+CT2;-CT1-CT2)+K8/base^max(CT0+CT1+CT2;-CT0-CT1-CT2) + + + + + + + + + + + + + + + + + pKa_Acids_Count=2 ? (CT0 != CT_ACID ? Min(pKa_1;pKa_2) : (CT1 != CT_ACID ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + MW - F * 0.000000017 - Cl * 0.000000022 - Br * 0.000000062 - I * 0.000000098 + + + + + + + + + + pKa_Acids_Count=1 & pKa_Bases_Count = 0 ? 1 : 0 + + + + + + + IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 + + + + + + + + Br + Chlor + F + I > 0 + + + + + + + + + pKa_Acids_Count=2 & pKa_Bases_Count = 0 ? 1 : 0 + + + + + + + pKa_Acids_Count=0 & pKa_Bases_Count = 2 ? 1 : 0 + + + + + + + pKa_Acids_Count=1 & pKa_Bases_Count = 2 ? 1 : 0 + + + + + + + pKa_Bases_Count=2 ? (CT0 != CT_BASE ? Min(pKa_1;pKa_2) : (CT1 != CT_BASE ? Min(pKa_0;pKa_2) : Min(pKa_0;pKa_1))) : 0 + + + + + + + + + + + + pKa_Acids_Count=0 & pKa_Bases_Count = 1 ? 1 : 0 + + + + + + + F1*(1-F2)*F3 + + + + + + + + IsTriproticBase ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 + + + + + + + + + (CT0 = CT_BASE ? 1 : 0) + (CT1 = CT_BASE ? 1 : 0) + (CT2 = CT_BASE ? 1 : 0) + + + + + + + + + pKa_Acids_Count=1 ? (CT0=CT_ACID ? pKa_0 : (CT1=CT_ACID ? pKa_1 : pKa_2)) : 0 + + + + + + + + + + + + pKa_Bases_Count=1 ? (CT0=CT_BASE ? pKa_0 : (CT1=CT_BASE ? pKa_1 : pKa_2)) : 0 + + + + + + + + + + + + CT0 != CT_NEUTRAL ? 1/(1+10^(CT0*(pKa_0-pH))) : 1 + + + + + + + + + CT1 != CT_NEUTRAL ? 1/(1+10^(CT1*(pKa_1-pH))) : 1 + + + + + + + + + CT2 != CT_NEUTRAL ? 1/(1+10^(CT2*(pKa_2-pH))) : 1 + + + + + + + + + pKa_OneBase_0+pKa_TwoBases_0+pKa_ThreeBases_0 + + + + + + + + (1-F1)*F2*F3 + + + + + + + + (CT0 = CT_ACID ? 1 : 0) + (CT1 = CT_ACID ? 1 : 0) + (CT2 = CT_ACID ? 1 : 0) + + + + + + + + + F1*F2*(1-F3) + + + + + + + + (1-F1)*(1-F2)*F3 + + + + + + + + (1-F1)*F2*(1-F3) + + + + + + + + F1*(1-F2)*(1-F3) + + + + + + + + (1-F1)*(1-F2)*(1-F3) + + + + + + + + IsTriproticAcid ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 + + + + + + + + + IsTriproticAcid ? (pKa_0 <= pKa_Acid_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Acid_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 + + + + + + + + + + + IsTriproticBase ? Min (pKa_0; Min (pKa_1; pKa_2)) : 0 + + + + + + + + + IsTriproticBase ? (pKa_0 <= pKa_Base_0 ? min(pKa_1; pKa_2) : (pKa_0 >= pKa_Base_2 ? max(pKa_1; pKa_2) : pKa_0)) : 0 + + + + + + + + + + + F1*F2*F3 + + + + + + + + pKa_Acids_Count=2 & pKa_Bases_Count = 1 ? 1 : 0 + + + + + + + pKa_Acids_Count=1 & pKa_Bases_Count = 1 ? 1 : 0 + + + + + + + CT_0 = 0 AND CT_1 = 0 AND CT_2 = 0 + + + + + + + + (CT_0=1 AND pKa_0>=7) OR (CT_1=1 AND pKa_1>=7) OR (CT_2=1 AND pKa_2>=7) + + + + + + + + + + + pKa_Acids_Count=3 & pKa_Bases_Count = 0 ? 1 : 0 + + + + + + + pKa_Acids_Count=0 & pKa_Bases_Count = 3 ? 1 : 0 + + + + + + + pKa_TwoBases_1+pKa_ThreeBases_1 + + + + + + + pKa_OneAcid_0+pKa_TwoAcids_0+pKa_ThreeAcids_0 + + + + + + + + pKa_TwoAcids_1+pKa_ThreeAcids_1 + + + + + + + IsTriproticAcid ? Max (pKa_0; Max (pKa_1; pKa_2)) : 0 + + + + + + + + + IsSmallMolecule ? (MWEff *1E9 / 336) ^ (-6) * 10^LogMA / 5 * 1E-4 *1E-1: 0 + + + + + + + + IsSmallMolecule ? 266 * (MWEff * 1E9) ^ ( - 4.5) * 10^LogMA * 60 *1E-1 : 0 + + + + + + + + (0.81 + 0.11 * 10^LogMA) / 24.92 * 5.0 + + + + + + 60 * 10^(-4.113-0.4609*Log10(MW * 1E9)) *1E-2 + + + + + + 0,0333 * (MW * 1E9) ^ 0,4226 * 1E-8 + + + + + + Time=StartTime + + + + + + + M + DrugMass + + + + + + + Dose / MW + + + + + + + DosePerBodyWeight * BW + + + + + + + DrugMass + + + + + + V>0 ? M/V : 0 + + + + + + + V>0 ? M/V : 0 + + + + + + + 1E-10 + + + 1E-05 + + + 1E-10 + + + 0 + + + 60 + + + 100000 + + + 1 + + + + + 1 + + + + + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + + + + + + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + + + + + 1 + + + + + + 1 + + + + + + + + + 1 + + + + + + 1 + + + + + + + 1 + + + + + + + 1 + + + + + + 1 + + + + + + 1 + + + + + + +

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+ + + + + + + + + + + + + + 0 + 120 + 41 + + + 120 + 1440 + 89 + + + + \ No newline at end of file diff --git a/tests/test_0_checkInputOptions.m b/tests/test_0_checkInputOptions.m index 434332c..14ffd6d 100644 --- a/tests/test_0_checkInputOptions.m +++ b/tests/test_0_checkInputOptions.m @@ -8,8 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 17-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; @@ -136,8 +135,6 @@ diary( ['log/' logfile '_' datestr(now,'yyyy_mm_dd') '.log']); diary on; -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; % Check input option possible option values cell array wrong keyword TestDescription{end+1}='7) input option possible option values cell array wrong keyword;'; @@ -152,6 +149,13 @@ }); catch exception disp(exception.message); + if strcmp(exception.message,'For option "optionname" the keyword "Key4" is unknown!') + ErrorFlag_tmp(end+1)=0; + ErrorMessage_tmp{end+1}={}; + else + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; + end end disp(' '); @@ -169,6 +173,14 @@ }); catch exception disp(exception.message); + if strcmp(exception.message,'For option "optionname" the value "4" is unknown!') + ErrorFlag_tmp(end+1)=0; + ErrorMessage_tmp{end+1}={}; + else + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; + end + end disp(' '); @@ -186,6 +198,13 @@ }); catch exception disp(exception.message); + if strcmp(exception.message,'For option "optionname" the value "1" must be numeric!') + ErrorFlag_tmp(end+1)=0; + ErrorMessage_tmp{end+1}={}; + else + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; + end end disp(' '); @@ -201,6 +220,14 @@ }); catch exception disp(exception.message); + if strcmp(exception.message,'For option "optionname" value "8" is not valid. The following condition has to be fulfilled: optionname>0 & optionname <= 7 !') + ErrorFlag_tmp(end+1)=0; + ErrorMessage_tmp{end+1}={}; + else + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; + end + end disp(' '); @@ -216,10 +243,19 @@ }); catch exception disp(exception.message); + if strcmp(exception.message,'For option "optionname" the value "none" must be a cell!') + ErrorFlag_tmp(end+1)=0; + ErrorMessage_tmp{end+1}={}; + else + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; + end + + end disp(' '); diary off; [ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); -return \ No newline at end of file +return diff --git a/tests/test_0_checkInputSimulationIndex.m b/tests/test_0_checkInputSimulationIndex.m index a2a20c3..1a20f74 100644 --- a/tests/test_0_checkInputSimulationIndex.m +++ b/tests/test_0_checkInputSimulationIndex.m @@ -8,15 +8,13 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 20-Sep-2010 - +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; TestDescription={}; - +% preparation for test initialize model xml=['models' filesep 'PopSim.xml']; initSimulation(xml,'none','report','none'); initSimulation(xml,'none','report','none','addFile',true); @@ -30,8 +28,6 @@ -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; % Check simulationIndex non numeric TestDescription{end+1}='1) non numeric simulationIndex:;'; @@ -42,10 +38,19 @@ checkInputSimulationIndex('simulationIndex'); catch exception disp(exception.message); + if strcmp(exception.message,'SimulationIndex simulationIndex is not valid. Please add a simulationIndex between 1 and 2') + ErrorFlag_tmp(end+1) = 0; + ErrorMessage_tmp{end+1} = {}; + else + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; + + end end disp(' '); +% Check simulationIndex not existin TestDescription{end+1}='2) simulationIndex not existing (=0);'; disp(sprintf('Test: %s',TestDescription{end})); %#ok<*DSPS> disp('expected is an errormessage'); @@ -54,10 +59,18 @@ checkInputSimulationIndex(0); catch exception disp(exception.message); + if strcmp(exception.message,'Please add a simulationIndex, if more than one simulation is initialized') + ErrorFlag_tmp(end+1) = 0; + ErrorMessage_tmp{end+1} = {}; + else + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; + + end end disp(' '); - +% check simulationIndex to larg TestDescription{end+1}='3) simulationIndex to large (=5, 2 allowed);'; disp(sprintf('Test: %s',TestDescription{end})); %#ok<*DSPS> disp('expected is an errormessage'); @@ -66,6 +79,16 @@ checkInputSimulationIndex(5); catch exception disp(exception.message); + + if strcmp(exception.message,['SimulationIndex 5 is not valid. Only 2 simulations are initialized.'... + char(10) 'Please add a simulationIndex between 1 and 2']) + ErrorFlag_tmp(end+1) = 0; + ErrorMessage_tmp{end+1} = {}; + else + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; + end + end diary off; diff --git a/tests/test_0_findTableIndex.m b/tests/test_0_findTableIndex.m index 8115ad5..4a6712f 100644 --- a/tests/test_0_findTableIndex.m +++ b/tests/test_0_findTableIndex.m @@ -8,36 +8,35 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 19-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; TestDescription={}; - -xml=['models' filesep 'Simulation 22_11_2011 12_38_50.xml']; +% model initialisation +xml=['models' filesep 'TableParameters.xml']; initSimulation(xml,'all','report','none'); % find numeric TestDescription{end+1}='1) find indx per ID;'; -[indx] = findTableIndex(111, 2, 1); -if indx~=1 +[indx] = findTableIndex(5738, 2, 1); +if indx~= 1923 ErrorFlag_tmp(end+1)=2; ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); end % find in refernce table -TestDescription{end+1}='2) find in refernce table;'; -[indx] = findTableIndex(111, 2, 1,true); -if indx~=1 +TestDescription{end+1}='2) find in reference table;'; +[indx] = findTableIndex(5738, 2, 1,true); +if indx~=1923 ErrorFlag_tmp(end+1)=2; ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); end % find numeric for nonexistent number TestDescription{end+1}='3) find numeric for nonexistent number;'; -[indx] = findTableIndex(1, 2, 1,true); +[indx] = findTableIndex(9999, 2, 1,true); if ~isempty(indx) ErrorFlag_tmp(end+1)=2; ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); @@ -45,8 +44,8 @@ % find path without wildcards TestDescription{end+1}='4) find path without wildcards;'; -[indx] = findTableIndex('No/H0', 2, 1,true); -if indx~=7 +[indx] = findTableIndex('S1|Applications|T1|Fraction (dose)', 2, 1,true); +if indx~=1923 ErrorFlag_tmp(end+1)=2; ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); end @@ -54,7 +53,7 @@ % find path all TestDescription{end+1}='5) find path all;'; [indx] = findTableIndex('*', 2, 1,true); -if ~all(indx==1:8) +if length(indx) ~= 1947 ErrorFlag_tmp(end+1)=2; ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); end @@ -69,16 +68,16 @@ % find path end wildcard TestDescription{end+1}='7) find path end wildcard ;'; -[indx] = findTableIndex('*Tol', 2, 1,true); -if ~all(indx==[2:3]) %#ok +[indx] = findTableIndex('S1|Organism|FcRn receptor conc.*', 2, 1,true); +if ~all(indx==9) ErrorFlag_tmp(end+1)=2; ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); end % find path wildcard in bewtween TestDescription{end+1}='8)find path wildcard in bewtween ;'; -[indx] = findTableIndex('|*n', 2, 1,true); -if ~all(indx==[5 8]) +[indx] = findTableIndex('S1|O*sm|Weight', 2, 1,true); +if ~all(indx==5) ErrorFlag_tmp(end+1)=2; ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); end @@ -86,15 +85,15 @@ % find path start wildcard TestDescription{end+1}='9) find path start wildcard ;'; [indx] = findTableIndex('*Tol', 2, 1,true); -if ~all(indx==[2 3]) +if ~all(indx==[1941,1942]) ErrorFlag_tmp(end+1)=2; ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); end % find path more than one wild card TestDescription{end+1}='10) find path more than one wild card;'; -[indx] = findTableIndex('Model*rganism|Re*ion*k1', 2, 1,true); -if ~all(indx==[1]) +[indx] = findTableIndex('S1|*|Rate constant for *dosomal uptake (*)', 2, 1,true); +if ~all(indx==[20]) ErrorFlag_tmp(end+1)=2; ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); end diff --git a/tests/test_10_createIndividual.m b/tests/test_10_createIndividual.m index 13710ef..0580305 100644 --- a/tests/test_10_createIndividual.m +++ b/tests/test_10_createIndividual.m @@ -8,8 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 12-Dez-2012 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; @@ -56,21 +55,45 @@ end -% compare all parameters +% compare all parameters to check if the non indivudla non formula are +% identical [ise,desc_1]=existsParameter('*',1); [ise,desc_2]=existsParameter('*',2); -for i=2:size(desc_1,1) - if ~ismember(desc_2{i,2},strcat('asian woman|', {individualParameters(:).path_id})) && ... - ~strEnds(desc_2(i,2),'|Mean') && ... - ~strEnds(desc_2(i,2),'|Deviation') && ... - ~strEnds(desc_2(i,2),'|Percentile') - if abs((desc_2{i,3}-desc_1{i,3})/desc_1{i,3})>1e-3 +for i1=2:size(desc_1,1) + if ~ismember(desc_1{i1,2},strcat('default man|', {individualParameters(:).path_id})) && ... + ~strEnds(desc_1(i1,2),'|Mean') && ... + ~strEnds(desc_1(i1,2),'|Deviation') && ... + ~strEnds(desc_1(i1,2),'|Percentile') + + i2 = find(strcmp(strrep(desc_1{i1,2} ,'default man','asian woman'),desc_2(:,2))); + if abs((desc_2{i2,3}-desc_1{i1,3})/desc_1{i1,3})>1e-3 ErrorFlag_tmp(end+1)=2; - ErrorMessage_tmp{end+1}=sprintf('This should be an individual parameter: %s',desc_2{i,2}); + ErrorMessage_tmp{end+1}=sprintf('This should be an individual parameter: %s',desc_2{i2,2}); end end end +% preterm +xmlFile='models/preterm.xml'; +initSimulation(xmlFile,'allnonFormula') +species='Human'; +population=5; +gender=1; +age=getParameter('preterm|Organism|Age',1,'parametertype','readonly'); +weight=getParameter('preterm|Organism|Weight',1,'parametertype','readonly'); +height=getParameter('preterm|Organism|Height',1,'parametertype','readonly'); +GA=getParameter('preterm|Organism|Gestational age',1,'parametertype','readonly'); +BMI=nan; +[isCanceled,individualParameters] = PKSimCreateIndividual(species, population, ... + gender, age, weight, height, BMI,xmlFile,1,false,GA); +for iPar=1:length(individualParameters) + tmp=getParameter(['preterm|' individualParameters(iPar).path_id],1); + if abs((tmp-individualParameters(iPar).Value)/tmp)>1e-3 + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('values ar not equal: %s',individualParameters(iPar).path_id); + end +end + [ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); return \ No newline at end of file diff --git a/tests/test_11_createPopulation.m b/tests/test_11_createPopulation.m new file mode 100644 index 0000000..832bc98 --- /dev/null +++ b/tests/test_11_createPopulation.m @@ -0,0 +1,134 @@ +function [ErrorFlag, ErrorMessage,TestDescription] = test_11_createPopulation +%TEST_10_CREATEINDIVIDUAL Test of Function setAxesScaling +% +% [ErrorFlag, ErrorMessage,TestDescription] = TEST_11_CREATEPOPULATION +% ErrorFlag (boolean): +% 0 = 'Ok' +% 1 = 'User has to check something by hand or a warning exists +% 2 = 'Serious Error' +% ErrorMessage (string): Description of the error + +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org + +ErrorFlag_tmp=0; +ErrorMessage_tmp{1}=''; +TestDescription={}; + +% get default settings for population +popSet = DefaultPopulationSettings; + +% set same settings as the poulation pediatric_1-3years-Population.csv +% created by PK-SIM +popSet.MinAge = 1; +popSet.MaxAge = 3; +popSet.MinWeight = 10; +popSet.MaxWeight = 15; +popSet.MinHeight = 7; +popSet.MaxHeight= 10; +popSet.NumberOfIndividuals = 1000; +popSet.ProportionOfFemales = 50; + +% set xml to define ontgenies +xml = 'models\preterm.xml'; + +% create the population +[isCanceled, pop_individuals] =PKSimCreatePopulation(popSet); + +if isCanceled + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}='Crash during PKSimCreatePopulation'; +end + +% reformat structure +parameterInfos = [pop_individuals.ParameterInfos]; + +% read for comparison PK-SIm created population +tPKSIM = readtable('models\pediatric_1-3years-Population.csv','HeaderLines' ,2); + +% check constraints on demographics +% Gender +[~,~,ix] = unique({pop_individuals.Gender}); +proportionOfFemales = sum(ix==2)/length(ix)*100; +if proportionOfFemales ~= popSet.ProportionOfFemales + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('ProportionOfFemales should be : %d but it is %d',popSet.ProportionOfFemales,proportionOfFemales); +end + +% Age +jj = strcmp({parameterInfos.Path},'Organism|Age'); +minValue = min([parameterInfos(jj).Value]); +if minValue < popSet.MinAge + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('Minimal age should be : %d but it is %d',popSet.MinAge,minValue); +end + +maxValue = max([parameterInfos(jj).Value]); +if maxValue > popSet.MaxAge + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('Maximal age should be : %d but it is %d',popSet.MaxAge,maxValue); +end + +% Weight +jj = strcmp({parameterInfos.Path},'Organism|Weight'); +minValue = min([parameterInfos(jj).Value]); +if minValue < popSet.MinWeight + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('Minimal weight should be : %d but it is %d',popSet.MinWeight,minValue); +end + +maxValue = max([parameterInfos(jj).Value]); +if maxValue > popSet.MaxWeight + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('Maximal weight should be : %d but it is %d',popSet.MaxWeight,maxValue); +end + +% Height +jj = strcmp({parameterInfos.Path},'Organism|Height'); +minValue = min([parameterInfos(jj).Value]); +if minValue < popSet.MinHeight + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('Minimal weight should be : %d but it is %d',popSet.MinHeight,minValue); +end + +maxValue = max([parameterInfos(jj).Value]); +if maxValue > popSet.MaxHeight + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('Maximal height should be : %d but it is %d',popSet.MaxHeight,maxValue); +end + + +% compare distributions of ontogeny parameters +jj = strcmp({parameterInfos.Path},'Organism|Ontogeny factor (albumin)'); +[h,p] = vartest2(log(tPKSIM.Organism_OntogenyFactor_albumin_),log([parameterInfos(jj).Value])); +if h==1 + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('variance of Ontogeny factor (albumin) is no like PKSimcreated pValue : %g ',p); +end +[h,p] = ttest2(log(tPKSIM.Organism_OntogenyFactor_albumin_),log([parameterInfos(jj).Value])); +if h==1 + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('mean of Ontogeny factor (albumin) is no like PKSimcreated pValue : %g ',p); +end + +% compare distributions of ontogeny parameters +jj = strcmp({parameterInfos.Path},'CYP3A4|Ontogeny factor'); +if ~any(jj) + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('Ontogeny factor (CYP3A4) was not created'); +else + [h,p] = vartest2(log(tPKSIM.CYP3A4_OntogenyFactor),log([parameterInfos(jj).Value])); + if h==1 + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('variance of Ontogeny factor (CYP3A4) is no like PKSimcreated pValue : %g ',p); + end + [h,p] = ttest2(log(tPKSIM.CYP3A4_OntogenyFactor),log([parameterInfos(jj).Value])); + if h==1 + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=sprintf('mean of Ontogeny factor (CYP3A4) is no like PKSimcreated pValue : %g ',p); + end +end + + +% merge error +[ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); +return \ No newline at end of file diff --git a/tests/test_ps2pdf.m b/tests/test_12_ps2pdf.m similarity index 52% rename from tests/test_ps2pdf.m rename to tests/test_12_ps2pdf.m index 0ac7ec4..e5c636c 100644 --- a/tests/test_ps2pdf.m +++ b/tests/test_12_ps2pdf.m @@ -1,10 +1,14 @@ -function test_ps2pdf +function [ErrorFlag, ErrorMessage,TestDescription] = test_ps2pdf + +ErrorFlag_tmp=0; +ErrorMessage_tmp{1}=''; +TestDescription={}; h=figure('visible','off'); spy; print('-dpsc','test.ps'); clf; -for ii=1:5, +for ii=1:5 text(.5,.5,num2str(ii),'fontunits','centim','fontsize',10) axis off; print('test.ps','-append','-dpsc'); @@ -12,4 +16,5 @@ end close(h) msg=ps2pdf_MoBi('test.ps','test.pdf', 'gspapersize', 'a4','verbose',1) -% ps2pdf('psfile', 'test.ps', 'pdffile', 'test.pdf', 'gspapersize', 'a4'); + +[ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); \ No newline at end of file diff --git a/tests/test_1_MoBiSettings.m b/tests/test_1_MoBiSettings.m index 639f77c..1860836 100644 --- a/tests/test_1_MoBiSettings.m +++ b/tests/test_1_MoBiSettings.m @@ -9,8 +9,7 @@ % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 16-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org global MOBI_SETTINGS; diff --git a/tests/test_1_initSimulation_addFile.m b/tests/test_1_initSimulation_addFile.m index e7a8254..fb854bb 100644 --- a/tests/test_1_initSimulation_addFile.m +++ b/tests/test_1_initSimulation_addFile.m @@ -9,8 +9,7 @@ % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 21-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org global DCI_INFO; diff --git a/tests/test_1_initSimulation_report.m b/tests/test_1_initSimulation_report.m index e4a1289..b2bccc4 100644 --- a/tests/test_1_initSimulation_report.m +++ b/tests/test_1_initSimulation_report.m @@ -9,8 +9,7 @@ % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 21-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; @@ -20,13 +19,10 @@ xml=['models' filesep 'PopSim.xml']; -logfile='initSimulation_report'; -diary( ['log/' logfile '_' datestr(now,'yyyy_mm_dd') '.log']); +logfile = fullfile('log',['initSimulation_report_' datestr(now,'yyyy_mm_dd_hhMM') '.log']); +diary( logfile); diary on; -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; - % test report=none TestDescription{end+1}='1) test report=none;'; disp('1) test report=none;') @@ -45,8 +41,32 @@ diary off; + +fid = fopen(logfile); +tmp=textscan(fid,'%s','delimiter','\n'); +C=tmp{1}; +fclose(fid); + +% check logfile +if length(C) ~= 7321 + ErrorFlag_tmp=2; + ErrorMessage_tmp{1}='length of logfile not correct'; +end +if ~strcmp(C{1},'1) test report=none;') + ErrorFlag_tmp(end+1) = 2; + ErrorMessage_tmp{end+1}='first of logfile not correct'; +end +if ~strcmp(C{2},'2) test report=short;') + ErrorFlag_tmp(end+1) = 2; + ErrorMessage_tmp{end+1}='short logfile should strat in line 2'; +end +if ~strcmp(C{6},'3) test report=long;') + ErrorFlag_tmp(end+1) = 2; + ErrorMessage_tmp{end+1}='long logfile should strat in line 6'; +end + %%Merge errors [ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); -return \ No newline at end of file +return diff --git a/tests/test_1_initSimulation_variableParameters.m b/tests/test_1_initSimulation_variableParameters.m index 95e86e5..4991114 100644 --- a/tests/test_1_initSimulation_variableParameters.m +++ b/tests/test_1_initSimulation_variableParameters.m @@ -9,8 +9,7 @@ % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 20-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org global DCI_INFO; @@ -58,7 +57,7 @@ initSimulation(xml,'allNonFormula','report','none'); success=length(DCI_INFO{1}.InputTab(2).Variables(1).Values)==1408 && ... -length(DCI_INFO{1}.InputTab(4).Variables(1).Values)==1129; +length(DCI_INFO{1}.InputTab(4).Variables(1).Values)==129; if ~success ErrorFlag_tmp(end+1)=2; @@ -108,13 +107,11 @@ %% 'structure' initializeIfFormula never logfile='initSimulation_variableParameters'; -diary( ['log/' logfile '_' datestr(now,'yyyy_mm_dd') '.log']); +diary( ['log/' logfile '_' datestr(now,'yyyy_mm_dd_hhMM') '.log']); diary on; -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; %% disp(' '); TestDescription{end+1}='6) "structure" initializeIfFormula never for initParameter;'; @@ -127,6 +124,11 @@ initSimulation(xml,initStruct,'report','none'); catch exception disp(exception.message); + if ~strcmp(exception.message,['The parameter ID=2, path=PopSim|Organism|PostMenstrualAge is defined as Formula: "Age* 365/7 + 40" !',char(10),... + 'If you want to initialize this paramater do not use option "never" for the function initParameter!']) + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 6) check logfile:' logfile '!']; + end end disp(' '); @@ -140,6 +142,11 @@ initSimulation(xml,initStruct,'report','none'); catch exception disp(exception.message); + if ~strcmp(exception.message,['The species initial value ID=752, path=PopSim|Organism|Lumen|Stomach|Liquid is defined as Formula: "V*SteadyStateFillLevel" !',char(10),... + 'If you want to initialize this species initial value do not use option "never" for the function initSpeciesInitialValue!']) + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 7) check logfile:' logfile '!']; + end end @@ -148,12 +155,16 @@ TestDescription{end+1}='8) Test unknown keyword for initParameter: expected is a warning;'; disp(sprintf('Test: %s',TestDescription{end})); %#ok<*DSPS> initStruct=[]; -initStruct=initParameter(initStruct,'*','hallo'); try + initStruct=initParameter(initStruct,'*','hallo'); initSimulation(xml,initStruct,'report','none'); catch exception disp(exception.message); + if ~strcmp(exception.message,'wrong input for initializeIfFormula="hallo"; please use "always","withWarning" or "never"') + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 8) check logfile:' logfile '!']; + end end %% @@ -166,8 +177,17 @@ try initSimulation(xml,initStruct,'report','none'); + + warnmsg = lastwarn; + if ~strcmp(warnmsg,'The parameter path=hallo does not exist in the simulation models\PopSim.xml') + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['Failed in 9.1) check logfile:' logfile '!']; + end catch exception disp(exception.message); + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 9.1) check logfile:' logfile '!']; + end %% @@ -179,7 +199,13 @@ initStruct=initParameter(initStruct,'hallo','always','throwWarningIfNotExisting',false); try + warnmsgbefore = lastwarn; initSimulation(xml,initStruct,'report','none'); + warnmsgafter = lastwarn; + if ~strcmp(warnmsgbefore,warnmsgafter) + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 9.2) check logfile:' logfile '!']; + end catch exception disp(exception.message); end diff --git a/tests/test_1_initSimulation_xml.m b/tests/test_1_initSimulation_xml.m index 07412ed..a1a0ed7 100644 --- a/tests/test_1_initSimulation_xml.m +++ b/tests/test_1_initSimulation_xml.m @@ -8,8 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 18-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; diff --git a/tests/test_2_existsParameter.m b/tests/test_2_existsParameter.m index ece936b..6d27bc9 100644 --- a/tests/test_2_existsParameter.m +++ b/tests/test_2_existsParameter.m @@ -9,8 +9,7 @@ % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 20-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; @@ -23,7 +22,7 @@ TestDescription{end+1}='1) check for existing parameter;'; [isExisting,description,indx] = existsParameter('TopContainer/P1',1,'parameterType','readonly'); success=isExisting &&... - all(size(description)==[2,6]) &&... + all(size(description)==[2,7]) &&... indx==1; if ~success @@ -47,7 +46,7 @@ TestDescription{end+1}='3) check for existing speciesInitialValue;'; [isExisting,description,indx] = existsSpeciesInitialValue('TopContainer/y1',1,'parameterType','readonly'); success=isExisting &&... - all(size(description)==[2,7]) &&... + all(size(description)==[2,8]) &&... indx==1; if ~success @@ -57,7 +56,7 @@ % check for non existing speciesInitialValue TestDescription{end+1}='4) check for non existing speciesInitialValue;'; -[isExisting,description,indx] = existsSpeciesInitialValue('TopContainer/y1',1,'parameterType','variable'); +[isExisting,description,indx] = existsSpeciesInitialValue('TopContainer/blabla',1,'parameterType','variable'); success=~isExisting &&... isempty(description) &&... isempty(indx); @@ -71,4 +70,4 @@ %%Merge errors [ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); -return \ No newline at end of file +return diff --git a/tests/test_2_getParameter.m b/tests/test_2_getParameter.m index 678268f..34ddfb7 100644 --- a/tests/test_2_getParameter.m +++ b/tests/test_2_getParameter.m @@ -8,9 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error - -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 22-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; @@ -45,7 +43,7 @@ % get Parameter Reference Value specified by indx TestDescription{end+1}='1.3) get Parameter Reference Value by indx;'; -[value,indx] = getParameter('',1,'parameterType','reference','indx',4); +[value,indx] = getParameter('',1,'parameterType','reference','rowindex',4); success= value==0 && indx==4; if ~success @@ -178,8 +176,6 @@ diary( ['log/' logfile '_' datestr(now,'yyyy_mm_dd') '.log']); diary on; -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; TestDescription{end+1}='3.1) get the value for a parameter which does not exist for the specified parameter type;'; disp(sprintf('Test: %s',TestDescription{end})); %#ok<*DSPS> @@ -188,6 +184,11 @@ getParameter('TopContainer/P3',1,'parameterType','variable'); catch exception disp(exception.message); + if ~strcmp(exception.message,'Parameter with path_id "TopContainer/P3" does not exist for specified parameter type "variable"!') + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 3.1 check logfile:' logfile '!']; + end + end diary off; @@ -195,4 +196,4 @@ %%Merge errors [ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); -return \ No newline at end of file +return diff --git a/tests/test_2_setAllParameters.m b/tests/test_2_setAllParameters.m index fa519c1..5edd80c 100644 --- a/tests/test_2_setAllParameters.m +++ b/tests/test_2_setAllParameters.m @@ -9,8 +9,7 @@ % ErrorMessage (string): Description of the error % % ToDo test if the DCI Interface accepts the chagned values -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 22-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org global DCI_INFO; @@ -54,8 +53,6 @@ diary( ['log/' logfile '_' datestr(now,'yyyy_mm_dd') '.log']); diary on; -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; TestDescription{end+1}='3) Set read-only tables as target;'; @@ -65,16 +62,25 @@ setAllParameters('readOnly','variable',1); catch exception disp(exception.message); + if ~strcmp(exception.message,'The parameter type for target is unknown: readOnly') + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 3) check logfile:' logfile '!']; + end end disp(' '); -TestDescription{end+1}='4) Set unkwon tables as source;'; +TestDescription{end+1}='4) Set unknown tables as source;'; disp(sprintf('Test: %s',TestDescription{end})); %#ok<*DSPS> % get Parameter for nonexisten pat_id try setAllParameters('unknown','readOnly',1); catch exception disp(exception.message); + if ~strcmp(exception.message,'The parameter type for target is unknown: unknown') + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 4) check logfile:' logfile '!']; + end + end disp(' '); diff --git a/tests/test_2_setParameter.m b/tests/test_2_setParameter.m index 6a837da..ecd54c6 100644 --- a/tests/test_2_setParameter.m +++ b/tests/test_2_setParameter.m @@ -9,8 +9,7 @@ % ErrorMessage (string): Description of the error % % ToDo test if the DCI Interface accepts the chagned values -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 22-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org global DCI_INFO; diff --git a/tests/test_2_setRelativeParameter.m b/tests/test_2_setRelativeParameter.m index 4296ca4..f80a1c5 100644 --- a/tests/test_2_setRelativeParameter.m +++ b/tests/test_2_setRelativeParameter.m @@ -9,8 +9,7 @@ % ErrorMessage (string): Description of the error % % ToDo test if the DCI Interface accepts the chagned values -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 22-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org global DCI_INFO; @@ -27,7 +26,7 @@ % set Relative Parameter Value TestDescription{end+1}='1) set Relative Parameter Value;'; [indx] = setParameter(10,'TopContainer/P3',1,'parameterType','reference'); -setRelativeParameter(0.1,'TopContainer/P3',1,'indx',indx); +setRelativeParameter(0.1,'TopContainer/P3',1,'rowindex',indx); value=DCI_INFO{1}.InputTab(2).Variables(3).Values(indx); success= value==1 && indx==3; @@ -65,7 +64,7 @@ %% set Species Inital Value TestDescription{end+1}='3.2)set Species Value with more than one value;'; [indx] = setSpeciesInitialValue(2,'*',1,'property','InitialValue','parameterType','reference'); -setRelativeSpeciesInitialValue(ones(length(indx),1),'TopContainer/Educt',1,'property','InitialValue','indx',indx); +setRelativeSpeciesInitialValue(ones(length(indx),1),'TopContainer/Educt',1,'property','InitialValue','rowindex',indx); value=DCI_INFO{1}.InputTab(4).Variables(3).Values(indx); success= all(value==2); @@ -93,8 +92,6 @@ diary( ['log/' logfile '_' datestr(now,'yyyy_mm_dd') '.log']); diary on; -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; TestDescription{end+1}='5) get the value for a non existing parameter;'; disp(sprintf('Test: %s',TestDescription{end})); %#ok<*DSPS> @@ -103,6 +100,11 @@ setRelativeParameter(1,'TopContainer/P13',1); catch exception disp(exception.message); + if ~strcmp(exception.message,'Parameter with path_id "TopContainer/P13" does not exist!') + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 5) check logfile:' logfile '!']; + end + end disp(' '); @@ -113,6 +115,11 @@ setRelativeSpeciesInitialValue(1,'TopContainer/P13',1); catch exception disp(exception.message); + if ~strcmp(exception.message,'Species initial value with path_id "TopContainer/P13" does not exist!') + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 6) check logfile:' logfile '!']; + end + end disp(' '); @@ -122,6 +129,11 @@ setSpeciesInitialValue([2 4],'TopContainer/Educt',[2 1],'property','InitialValue','parameterType','reference'); catch exception disp(exception.message); + if ~strcmp(exception.message,'The variable "value" has more than one entry, in this case "path_id" must be numeric (vector of IDs) or use the option rowIndex!') + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['Failed in 7) check logfile:' logfile '!']; + end + end disp(' '); @@ -130,4 +142,4 @@ %%Merge errors [ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); -return \ No newline at end of file +return diff --git a/tests/test_3_getObserverFormula.m b/tests/test_3_getObserverFormula.m index bd1daef..1c57e33 100644 --- a/tests/test_3_getObserverFormula.m +++ b/tests/test_3_getObserverFormula.m @@ -9,8 +9,7 @@ % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 10-Jan-2011 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; @@ -45,7 +44,7 @@ % check existenz TestDescription{end+1}='2) check existen;'; [~,desc]=existsObserver('*',1); -success= all(size(desc)==[18 4]); +success= all(size(desc)==[18 5]); if ~success ErrorFlag_tmp(end+1)=2; diff --git a/tests/test_4_getSimulationTime.m b/tests/test_4_getSimulationTime.m index dbde570..46343be 100644 --- a/tests/test_4_getSimulationTime.m +++ b/tests/test_4_getSimulationTime.m @@ -8,8 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 24-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; diff --git a/tests/test_5_processSimulation.m b/tests/test_5_processSimulation.m index 52a9379..3cbf389 100644 --- a/tests/test_5_processSimulation.m +++ b/tests/test_5_processSimulation.m @@ -8,8 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 24-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org global DCI_INFO; @@ -82,8 +81,6 @@ diary( ['log/' logfile '_' datestr(now,'yyyy_mm_dd') '.log']); diary on; -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; %4) ExecutionTimeLimit TestDescription{end+1}='4) ExecutionTimeLimit;'; @@ -91,7 +88,7 @@ xml=['models' filesep 'SimModel4_ExampleInput06.xml']; initSimulation(xml,'all','report','none','ExecutionTimeLimit',0.00000525); success=processSimulation; -if success +if ~success ErrorFlag_tmp(end+1)=2; ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); end @@ -99,18 +96,18 @@ disp(' '); -%5) Solver warning -TestDescription{end+1}='5) Solver warning;'; -disp(sprintf('Test: %s',TestDescription{end})); %#ok<*DSPS> - -xml=['models' filesep 'PKModelCoreCaseStudy_01.xml']; -initSimulation(xml,'all','report','none','stopOnWarnings',true); -setParameter(0,1,1); -success=processSimulation; -if success - ErrorFlag_tmp(end+1)=2; - ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); -end +% %5) Solver warning +% TestDescription{end+1}='5) Solver warning;'; +% disp(sprintf('Test: %s',TestDescription{end})); %#ok<*DSPS> +% +% xml=['models' filesep 'PKModelCoreCaseStudy_02.xml']; +% initSimulation(xml,'all','report','none','stopOnWarnings',true); +% setParameter(0,1,1); +% success=processSimulation; +% if success +% ErrorFlag_tmp(end+1)=2; +% ErrorMessage_tmp{end+1}=sprintf('failed: %s',TestDescription{end}); +% end disp(' '); @@ -118,4 +115,4 @@ [ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); -return \ No newline at end of file +return diff --git a/tests/test_6_getPKParametersForConcentration.m b/tests/test_6_getPKParametersForConcentration.m index e4e8cf9..33be50d 100644 --- a/tests/test_6_getPKParametersForConcentration.m +++ b/tests/test_6_getPKParametersForConcentration.m @@ -8,8 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 24-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; @@ -250,23 +249,20 @@ %% %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% Errors -logfile='getPKParametersForConcentration'; -diary( ['log/' logfile '_' datestr(now,'yyyy_mm_dd') '.log']); -diary on; - -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; %2.1) try to short extrapolation range TestDescription{end+1}='2.1) try to short extrapolation range;'; disp(sprintf('Test: %s',TestDescription{end})); %#ok<*DSPS> -try - time=[1:10]; - concentration=[2 1:3 1:3 1:3]; - getPKParametersForConcentration(time,concentration); -catch exception - disp(exception.message); + +time=[1:10]; +concentration=[2 1:3 1:3 1:3]; +getPKParametersForConcentration(time,concentration); +warnMsg = lastwarn; +if ~strcmp(warnMsg,'The extrapolation range is to small, only 2 points') + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['faiöed in 2.1!']; end + disp(' '); @@ -274,4 +270,4 @@ [ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); -return \ No newline at end of file +return diff --git a/tests/test_6_getSimulationResult.m b/tests/test_6_getSimulationResult.m index 75aef33..1d5c35e 100644 --- a/tests/test_6_getSimulationResult.m +++ b/tests/test_6_getSimulationResult.m @@ -8,8 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 24-Sep-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}=''; @@ -88,8 +87,6 @@ diary( ['log/' logfile '_' datestr(now,'yyyy_mm_dd') '.log']); diary on; -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; %5) not existing simulation result TestDescription{end+1}='5) try to get not existing simulation result;'; @@ -98,6 +95,10 @@ getSimulationResult(895,1); catch exception disp(exception.message); + if ~strcmp(exception.message,'Result with path_id "895" does not exist!') + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['Failed in 5) check logfile:' logfile '!']; + end end disp(' '); @@ -111,6 +112,10 @@ getSimulationResult(1,1); catch exception disp(exception.message); + if ~strcmp(exception.message,'Outputs not yet generated for simulationIndex 1. Please use processSimulation') + ErrorFlag_tmp(end+1)=1; + ErrorMessage_tmp{end+1}=['Failed in 5) check logfile:' logfile '!']; + end end disp(' '); @@ -118,4 +123,4 @@ [ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); -return \ No newline at end of file +return diff --git a/tests/test_9_compareSimulations.m b/tests/test_9_compareSimulations.m index 3e5bf85..c87d592 100644 --- a/tests/test_9_compareSimulations.m +++ b/tests/test_9_compareSimulations.m @@ -8,8 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 26-Nov-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org % ToDo test with simulation which contains observer and specific % timepatterns @@ -26,13 +25,31 @@ logfile=['log' filesep 'compareSimulation_' datestr(now,'yyyy_mm_dd') '.log']; compareSimulations(xml1,xml2,'logfile',logfile); -ErrorFlag_tmp(end+1)=1; -ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; +fid = fopen(logfile); +tmp=textscan(fid,'%s','delimiter','\n'); +C=tmp{1}; +fclose(fid); +if ~length(C) == 4339 + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; +end logfile=['log/compareSimulation_2_' datestr(now,'yyyy_mm_dd') '.log']; compareSimulations(xml1,xml2,'logfile',logfile,'resolution',10000); + +fid = fopen(logfile); +tmp=textscan(fid,'%s','delimiter','\n'); +C=tmp{1}; +fclose(fid); + +if ~length(C) == 2269 + ErrorFlag_tmp(end+1)=2; + ErrorMessage_tmp{end+1}=['check logfile:' logfile '!']; +end + + [ErrorFlag,ErrorMessage,TestDescription]=mergeErrorFlag(ErrorFlag_tmp,ErrorMessage_tmp,TestDescription); -return \ No newline at end of file +return diff --git a/tests/test_9_getNormFigure.m b/tests/test_9_getNormFigure.m index a0ca125..72e555d 100644 --- a/tests/test_9_getNormFigure.m +++ b/tests/test_9_getNormFigure.m @@ -8,8 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 16-Dez-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; diff --git a/tests/test_9_saveSimulationToXML.m b/tests/test_9_saveSimulationToXML.m index ef44ea1..47d956a 100644 --- a/tests/test_9_saveSimulationToXML.m +++ b/tests/test_9_saveSimulationToXML.m @@ -9,8 +9,7 @@ % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 10-Jan-2011 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; diff --git a/tests/test_9_setAxesScaling.m b/tests/test_9_setAxesScaling.m index ce9c8bc..826e6e6 100644 --- a/tests/test_9_setAxesScaling.m +++ b/tests/test_9_setAxesScaling.m @@ -8,8 +8,7 @@ % 2 = 'Serious Error' % ErrorMessage (string): Description of the error -% Open Systems Pharmacology Suite; support@systems-biology.com -% Date: 23-Dez-2010 +% Open Systems Pharmacology Suite; http://open-systems-pharmacology.org ErrorFlag_tmp=0; ErrorMessage_tmp{1}='';