Pharmacokinetics of Nifedipine Slow Release Tablet in Mexican Subjects: Further Evidence for an Oxidation Polymorphism

Abstract

Nifedipine kinetics after ingestion of 20 mg slow release tablets were studied in 12 young, healthy, Mexican subjects. Plasma levels were determined by a nifedipine‐specific HPLC assay. Levels rose after drug administration reaching a maximum concentration of 48.7 ± 7.3 ng/ml in 2.1 ± 0.7 h (mean ± SEM). Concentrations then decayed with a terminal half‐life of 16.9 ± 3.1 hours. AUC was 526 ± 62 ng h/ml. Five individuals were fast and seven were slow nifedipine metabolizers, according to the AUC criterion proposed by Kleinbioesem and coworkers. Individual AUC/Dose values from this and from other two studies on oral nifedipine kinetics in Mexicans were cumulated and the frequency histogram and probit analyses were performed (N = 30). A bimodal distribution was clearly observed. Fast and slow metabolizers were distinguished as those subjects with AUC/Dose values either lower or higher than 22.5 ng h/ml mg. Unlike European populations, it appears that slow metabolization is more frequent in Mexicans. Data strongly support the hypothesis of the existence of a polymorphism concerning nifedipine disposition kinetics due to genetic basis.