Pharmacokinetic modelling of methotrexate from routine clinical data in patients with acute lymphoblastic leukemia

Pharmacokinetic modelling was performed in nonmem (version 6.1) using a dataset including 273 patients (aged 2 to 23 years) who received high-dose mtx (5 g/m2 per course) in long-term treatment. total 2582 methotrexate plasma concentrations were performed by fluorescence polarisation immunoassay (fpia). a three compartment open model with elimination from the central compartment described the pharmacokinetics of methotrexate. the most important covariates affecting the disposition of methotrexate were age (age,year),body weight (bw,kg),and creatinine clearance (clr,lb;1). the final model with exponential disposition of mtx was clearance (cl,lh-1) = (6.11 + wt*6.7310-2) + (1.0810-4* clr)* exp(1.9510-1),(v,1) = 10,8+(age * 9.310-2) *exp(9.110- 1),q(1h-1) = 2.0410- *wt. pharmacokinetic parameters (%cv) in this study were cl,8.72 lh′ (44 %); vi,17.49 1 (95%); v2,6.048 1(56%); v3,0.015 1 (52%). the model predictions in the qualification group were found to have no bias and satisfactory precision.