diff --git a/inst/models/pk_pegasparaginase_modified_wurthwein.json5 b/inst/models/pk_pegasparaginase_modified_wurthwein.json5 new file mode 100644 index 0000000..ec5458b --- /dev/null +++ b/inst/models/pk_pegasparaginase_modified_wurthwein.json5 @@ -0,0 +1,74 @@ +{ + "id": "pk_pegasparaginase_modified_wurthwein", + "ode_code": "\ + dAdt[0] = - (CLi/Vi + Qi/Vi) * A[0] \ + dAdt[1] = + (Qi/Vi)*A[0] - (CLi/Vi + Qi/Vi)*A[1] \ + dAdt[2] = + (Qi/Vi)*A[1] - (CLi/Vi + Qi/Vi)*A[2] \ + dAdt[3] = + (Qi/Vi)*A[2] - (CLi/Vi + Qi/Vi)*A[3] \ + dAdt[4] = + (Qi/Vi)*A[3] - (CLi/Vi + Qi/Vi)*A[4] \ + dAdt[5] = + (Qi/Vi)*A[4] - (CLi/Vi + Qi/Vi)*A[5] \ + dAdt[6] = + (Qi/Vi)*A[5] - (CLi/Vi + Qi/Vi)*A[6] \ + dAdt[7] = + (Qi/Vi)*A[6] - (CLi/Vi + Qi/Vi)*A[7] \ + dAdt[8] = + (Qi/Vi)*A[7] - (CLi/Vi + Qi/Vi)*A[8] \ + dAdt[9] = + (Qi/Vi)*A[8] - (CLi/Vi + Qi/Vi)*A[9] \ + dAdt[10] = + (Qi/Vi)*A[9] - (CLi/Vi + Qi/Vi)*A[10] \ + dAdt[11] = + (Qi/Vi)*A[10] - (CLi/Vi + Qi/Vi)*A[11] \ + dAdt[12] = + (Qi/Vi)*A[11] - (CLi/Vi + Qi/Vi)*A[12] \ + dAdt[13] = + (Qi/Vi)*A[12] - (CLi/Vi + Qi/Vi)*A[13] \ + CONC = (A[0] + A[1] + A[2] + A[3] + A[4]+ A[5] + A[6] + A[7] + A[8] + A[9] + A[10] + A[11] + A[12] + A[13])/Vi \ + dAdt[14] = CONC \ + ", + "pk_code": "\ + BSA = pow(((HT*WT)/3600),0.5) \ + if(AGE<=8) {CLAGE = 1 ;} \ + if(AGE>8) {CLAGE = 1 + 0.021*(AGE - 8.0) ;} \ + CLSEX = 1.0 * pow(1-0.077, 1-SEX) \ + RELCLCOV= CLAGE * CLSEX \ + CLi = (CL/24) * (1+1.44345*(BSA-0.79)) * RELCLCOV \ + Vi = V * (1+1.56498*(BSA-0.79)) \ + Qi = (Q/24) * (1+1.44345*(BSA-0.79)) \ + ", + "n_comp": 15, + "obs": { "variable": "CONC" }, + "dose": { "cmt": 1, "bioav": 1 }, + "covariates": [ "AGE","SEX","HT","WT"], + "variables": [ "CLi","Vi","Qi","CONC","RELCLCOV","BSA","CLAGE","CLSEX"], + "parameters" : { + "CL": 0.0517535, + "V" : 1.74477, + "Q" : 1.09894 + }, + "fixed": ["Q","V"], + "units": { + "CL": "L/d", + "V": "L/kg", + "Q": "L/d" + }, + "iiv": { + "CL": 0.8083081 + }, + "omega_matrix": [0.653362], + "iov": null, + "ruv": { + "prop": 0.221777, + "add": 0.102318 + }, + "misc": { + "model_type": "custom", + "linearity": "linear", + "timevarying_parameter": false, + "init_parameter": false + }, + "references": [ + { + "ref": "Würthwein et al. European Journal of Drug Metabolism and Pharmacokinetics. 2021", + "url": "https://link.springer.com/article/10.1007/s13318-021-00670-8#Sec181" + } + ], + "comments": [ + "Utilizing updated/simplified model from 2021 publication.", + "Removed IOV and specific occasion effects on CL & V, which were specific to the trial and not generalizable to real-world application.", + "Re-estimated IIV on CLP, which was much larger than original publication. Larger IIV is in line with literature and clinical understanding about high variability in peg-asparaginase PK." + ], + "version": "0.1.4" +}