B. Tranchand, S. Urien, C. J. Ardiet
Centre Leon Berard, Lyon Cedex 08, France
Introduction: The alkylating agent melphalan has been used for 30 years in a variety of malignant tumors. Previous pharmacokinetic studies of intravenous melphalan have demonstrated large interindividual variations in the pharmacokinetic parameters.
Aim of the study: The present study was conducted in order to estimate population pharmacokinetic parameters of melphalan, and to look at a relationship between the pharmacokinetic parameters and the following covariates: age, sex, weight, body, surface area, creatinine clearance, previous treatments.
Methods: Data were obtained from 41 patients who received a single dose of intravenous melphalan. The sampling schedule was as follows: prior to the administration of melphalan then 5, 10, 15, 30, 45, 60, 90, 120, 180 min. Melphalan was assayed by HPLC. Population analysis was performed using NONMEM and MP2. A biexponential pharmacokinetic model was chosen to describe the plasma level data, and the model was parametrized in terms of: Cl, V1, k12, k21. The effect of covariates on pharmacokinetic parameters was investigated.
Results: Results obtained from the two approaches NONMEM and MP2 were similar (parameter estimates, coefficient of variation):
The main significant relationships were found between weight and Cl and V1. Sex seems to have a significant effect on Cl. Validation of the model is currently being performed using further kinetics.
Reference: PAGE 4 () Abstr 642 [www.page-meeting.org/?abstract=642]
Poster: poster