Hoyo-Vadillo C, Castañeda-Hernández G, Herrera J E, Vidal-Gárate J, Moreno-Ramos A, Chávez F, Hong E
Depto. de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico City, Mexico.
J Clin Pharmacol. 1989 Sep;29(9):816-20. 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.
对12名年轻、健康的墨西哥受试者服用20毫克缓释片后的硝苯地平动力学进行了研究。通过硝苯地平特异性高效液相色谱法测定血浆水平。给药后血药浓度升高，在2.1±0.7小时（平均值±标准误）达到最大浓度48.7±7.3纳克/毫升。随后浓度下降，终末半衰期为16.9±3.1小时。曲线下面积（AUC）为526±62纳克·小时/毫升。根据Kleinbloesem及其同事提出的AUC标准，5人为快速硝苯地平代谢者，7人为慢速代谢者。汇总了本研究以及另外两项关于墨西哥人口服硝苯地平动力学研究中的个体AUC/剂量值，并进行了频率直方图和概率分析（N = 30）。明显观察到双峰分布。快速和慢速代谢者分别定义为AUC/剂量值低于或高于22.5纳克·小时/毫升·毫克的受试者。与欧洲人群不同，墨西哥人中慢速代谢似乎更为常见。数据有力地支持了由于遗传基础导致硝苯地平处置动力学存在多态性的假设。
