Population pharmacokinetic study of methotrexate in patients with lymphoid malignancy

Cancer Chemotherapy and Pharmacology
Demiana William FaltaosPhilippe Lechat

Abstract

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. 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. 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...Continue Reading

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Citations

Mar 30, 2012·Annals of Hematology·Benjamin KasendaGerald Illerhaus
Jun 14, 2013·Cancer Chemotherapy and Pharmacology·Jennifer L PauleyMary V Relling
Nov 23, 2006·Clinical Pharmacokinetics·Dolores AumenteMaria José García
Jul 10, 2008·Clinical Pharmacokinetics·Anthe S ZandvlietAlwin D R Huitema
Feb 1, 2007·Expert Opinion on Drug Discovery·Jeffrey S BarrettJohn T Mondick
Aug 19, 2010·British Journal of Clinical Pharmacology·Hélène BlascoChantal Le Guellec
Jan 18, 2014·British Journal of Clinical Pharmacology·Isabelle Benz-de BretagneChantal Le Guellec
Feb 15, 2017·Therapeutic Drug Monitoring·Jean-Baptiste WoillardChantal Barin-Le Guellec
Feb 6, 2020·Biopharmaceutics & Drug Disposition·Zheng-Yuan ShiDan Yan
Mar 9, 2011·Therapeutic Drug Monitoring·A Franciscus van der MeerCees Neef
Aug 4, 2021·CPT: Pharmacometrics & Systems Pharmacology·Félicien Le LouedecMélanie White-Koning

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