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- Title
Population pharmacokinetic study of methotrexate in patients with lymphoid malignancy.
- Authors
Faltaos, Demiana William; Hulot, Jean Sebastian; Urien, Saïk; Morel, Veronique; Kaloshi, Gentian; Fernandez, Christine; khe Hoang Xuan; Leblond, Veronique; Lechat, Philippe
- Abstract
Purpose: A population pharmacokinetic model was developed to describe dose-exposure relationships of methotrexate (MTX) in adults with lymphoid malignancy; this is in order to explore the interindividual variability in relationship with the different physiopathological variables. The final model was applied to the Bayesian estimation of MTX concentrations using two blood samples. Methods: Fifty-one patients receiving 136 courses of MTX (1–6 per patient) were included in this study. The data was analysed using NONMEM software. A linear two-compartment model with linear elimination best described the data. Setting mean parameters values and variabilities to population values, we obtained Bayesian prediction of MTX pharmacokinetic parameters and concentrations. The predictive performance was evaluated by comparing the Bayesian estimated and observed concentrations and the Bayesian estimated parameters with the individual final model estimated parameters. Results: The population pharmacokinetic parameters and the inter-subject variablities expressed as coefficient of variation were: the total body clearance CL, 7.1 l h−1 (22%), the volume of the central and peripheral compartments V1, 25.1 l (22.5%), V2, 2.7 l (64%), respectively, and the transfer constant Q, 2.7 (51%) l h−1. Inter-course variability was only significant on CL. Age and serum creatinine had significant effects on CL and was included in the final model. A good correlation was obtained between Bayesian estimated and experimental concentrations ( r²=0.85).
- Subjects
PHARMACOKINETICS; METHOTREXATE; LYMPHOID tissue; PATHOLOGICAL physiology; BAYES' estimation
- Publication
Cancer Chemotherapy & Pharmacology, 2006, Vol 58, Issue 5, p626
- ISSN
0344-5704
- Publication type
Article
- DOI
10.1007/s00280-006-0202-0