尼莫地平在健康男性国人中药物代谢动力学变异性

对２６名健康男性国人ｐｏ６０ｍｇ尼莫地平普通片后药代动力学进行研究．Ｃｍａｘ，Ｔｍａｘ，ｔ１／２，ＭＲＴ和ＡＵＣ分别为６９±３４μｇ·Ｌ－１，１．１±０．３ｈ，２．２±０．６ｈ．３３±０９ｈ和１８６±７３μｇ·ｈ·Ｌ－１．ＡＵＣ和Ｃｍａｘ有较大的个体差异．对ＡＵＣ值作频数和机率图分析结果表明存在双态分布．提示尼莫地平药代动力学存在多态性．根据ＡＵＣ值大小，将受试者分成快代谢型和慢代谢型两类，结果显示受试者大多（２４／２６）属于快代谢型（ＡＵＣ＞３００μｇ·ｈ·Ｌ－１）．

Variability of nimodipine pharmacokinetics in healthy Chinese males

The pharmacokinetics of nimodipine (Nim) tablet in 26 healthy Chinese males was studied after an oral dose of 60 mg. Pharmacokinetic parameters for T_max, C_max, t_1/2, MRT and AUC were estimated as follows. T_max 1.1±0.3 h, C_max 69±34 μg·L^-1, t_1/2 2.2±0.6 h, MRT 3.3±0.9 h, and AUC 186±74 μg·h·L^-1. There were large intersubject variabilities in both AUC and C_max. When individual AUC values were cumulated and the frequency histogram and probit analysis were performed, a bimodal distribution was observed. The result indicated the hypothesis of the existence of a polymorphism concerning Nim disposition kinetics. The individuals were grouped as fast and slow metabolizers according to the AUC values. High frequency (24/26) of fast metabolizers was found (AUC>300 μg·L^-1).