Aims: A population pharmacokinetic model was developed to describe dose-response Relationships ofmethotrexate (MTX) in adults with breast cancer; this is done in order to explore interindividual variability inrelationships with different pathophysiological variables. Methods: Forty-five patients receiving 122 coursesof MTX (2-3 per patient) were included and data were analyzed using NONMEM software. A linear twocompartmentmodel with linear elimination best described the data. The predictive performance was evaluatedby comparing the predicted and observed concentrations and the population estimated parameters with theindividual estimated parameters. Results :The population pharmacokinetic parameters CL ,V1,Q, V2,K,K12and 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 1.30h-1 respectively. No covariate had significant effects on CL and VD. Conclusions: The results of this study combinerelationships between the pharmacokinetic parameters of MTX and patient covariates that may be useful fordose adjustment, with a convenient sampling procedure that may aid in optimizing cancer patient care.
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