ABSTRACT
AIMS: A population pharmacokinetic model was developed to describe dose-response Relationships of methotrexate (MTX) in adults with breast cancer; this is done in order to explore interindividual variability in relationships with different pathophysiological variables. METHODS: Forty-five patients receiving 122 courses of MTX (2-3 per patient) were included and data were analyzed using NONMEM software. A linear two-compartment model with linear elimination best described the data. The predictive performance was evaluated by comparing the predicted and observed concentrations and the population estimated parameters with the individual estimated parameters. RESULTS: The population pharmacokinetic parameters CL ,V1,Q, V2,K,K12 and K21 generated in NONMEM, using the FO method were 3.5 L/h,1.25 L,8.43 L/h,6.45 L, 2.8,6.74 and 1.30 h-1 respectively. No covariate had significant effects on CL and VD. CONCLUSIONS: The results of this study combine relationships between the pharmacokinetic parameters of MTX and patient covariates that may be useful for dose adjustment, with a convenient sampling procedure that may aid in optimizing cancer patient care.