Pharmacokinetics of nifedipine slow release tablet in Mexican subjects: further evidence for an oxidation polymorphism

• Published in: Journal of clinical pharmacology Vol. 29; no. 9; p. 816
• Main Authors: Hoyo-Vadillo, C, Castañeda-Hernández, G, Herrera, J E, Vidal-Gárate, J, Moreno-Ramos, A, Chávez, F, Hong, E
• Format: Journal Article
• Language: English
• Published: England 01.09.1989
• Subjects: Adult; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Humans; Male; Mexico; Nifedipine - administration & dosage; Nifedipine - blood; Nifedipine - pharmacokinetics; Oxidation-Reduction; Phenotype; Vasodilation - drug effects; Mexico
• ISSN: 0091-2700
• DOI: 10.1002/j.1552-4604.1989.tb03425.x

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 Kleinbloesem 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.