Cancer chemotherapy and pharmacology
-
Cancer Chemother. Pharmacol. · Apr 2006
Population pharmacokinetic analysis of ten phase II clinical trials of pemetrexed in cancer patients.
The objectives of these population pharmacokinetic analyses were to (1) assess the overall disposition of pemetrexed, (2) characterize between-patient and within-patient variability and identify influential covariates with respect to pemetrexed pharmacokinetics; and, (3) provide individual empirical Bayesian estimates of pharmacokinetic parameters for use in a subsequent pharmacokinetic/pharmacodynamic evaluation of neutropenia following pemetrexed administration. ⋯ Total systemic exposure (AUC) for a given dose of pemetrexed increases as renal function decreases. Since pharmacodynamic analyses have shown that AUC and not C (max) is the primary determinant of neutropenic response to pemetrexed, this suggests that dose adjustments based on renal function, rather than body surface area, might be considered for pemetrexed.