Pharmacokinetics of nifedipine slow release tablet in Mexican subjects: further evidence for an oxidation polymorphism.
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.
Hoyo-Vadillo
C
C
Depto. de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico City, Mexico.
Castañeda-Hernández
G
G
Herrera
J E
JE
Vidal-Gárate
J
J
Moreno-Ramos
A
A
Chávez
F
F
Hong
E
E
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D006801:Humans; D008297:Male; D008800:Mexico; D009543:Nifedipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D010641:Phenotype; D014664:Vasodilation / Q000187:drug effects
D003692:Delayed-Action Preparations; D009543:Nifedipine