[Pharmacokinetics of methotrexate and therapeutic drug monitoring in children with osteosarcoma. Computer simulation using a pharmacokinetic model].

The pharmacokinetics of methotrexate (MTX) and the therapeutic drug monitoring (TDM) in children treated-with high-dose of MTX (HD MTX) have been discussed. The pharmacokinetics of MTX was studied in 15 children (54 courses) with osteosarcoma, treated with HD MTX (8, 10 and 12 g/m2; 4 h i.v. infusion). Pharmacokinetic analysis was performed by standard non-compartmental methods and using two-compartment nonlinear model with coexistence of additional, parallel linear route of elimination from the central compartment. This proposed model can be used for computer simulation and prognosis of the serum-level curve course depending on the simulated dosage, enhanced diuresis and simulated kidney or liver insufficiency during the dose individualisation. The usage of the pharmacokinetic model for computer simulations may improve the understanding of MTX kinetics and can optimalise dosage regimens for the next cycles of chemotherapy.