Bayesian Estimation and Population Pharmacokinetic Parameters of High Dose Methotrexate in Osteosarcoma

Abstract

High-dose methotrexate (H.D.M.T.X.) was given by a 4 h infusion (8 g.m⁻²) to 6 patients with osteosarcoma for a total of 15 chemotherapy courses. The pharmacokinetics of methotrexate, determined by F.P.I.A., was described by a two-compartment open model with elimination from the central compartment. Population pharmacokinetic parameters were obtained by non-linear regression from 8 data points for each course, and were subsequently used to fit the same data by the bayesian estimation method. Volume of distribution, clearance, elimination constant and distribution half-life were well predicted (± 10 %) by the bayesian method with only two points taken at the end of the infusion and 48 h after. The prediction was less good (± 25 %) for the transfer constants and the elimination half-life. This procedure enables the estimation of individual pharmacokinetic parameters for methotrexate at minimal cost and minimal disturbance for the patient.