CYP2D6表现型决定16名中国汉族受试者普罗帕酮对映体药物动力学的差异<英文>  

CYP2D6 phenotype determines pharmacokinetic variability of propafenone enantiomers in 16 HAN Chinese subjects

作　　者：蔡卫民[1] 陈冰[2] 蔡明虹[2] 张银娣 

机构地区：[1]南京医科大学临床药理研究所 [2]南京军区南京总医院临床药理科,南京中国210002

出　　处：《中国药理学报》1999年第8期720-724,共5页Acta Pharmacologica Sinica

基　　金：Project supported by the Army Medical Research Foundation of PLA, China (Grant № 96M023);by Research Finacial Aid for Overseas Scholar from the Ministry of Human Resources,China (Grant № 96HG01).

摘　　要：目的:研究CYP2D6表现型在汉族健康受试者普罗帕酮对映体代谢中的作用。方法:选取用右美沙芬进行代谢分型后得到的7名极快代谢者(VEM)和9名中速代谢者(IM)。单剂量口服消旋普罗帕酮400mg,抽取0-15h静脉血。运用反相高压液相色谱法加柱前衍生化,定量分析血浆中普罗帕酮对映体浓度。结果:两种CYP2D6表现型的S-Pro代谢均较R-Pro慢,血浆浓度升高。此外,IM中R-Pro的半衰期比R-Pro大,VEM无此差别。但是,Pro对映体在VEM和IM中的代谢有明显差异。IM组两种对映体的C_(max)和AUC均比VEM组大(P<0.05)。IM组Pro对映体的Cl仅为VEM组的一半[(67±17)vs(133±28)L·h^(-1)for S-Pro,(90±24)vs(200±87)L·h^(-1)for R-Pro,P<0.0]。T_(1/2),T_(max),C_(max),Cl和AUC的S/R比值无显著差异(P>0.05)。结论:CYP2D6表现型决定了普罗帕酮对映体的药动学差异,EM受试者中IM的存在也许与中国人CYP2D6酶活性下降有关。AIM: To determine the role of the CYP2D6 phenotype in the metabolism of propafenone (Pro) enantiomers in 16 HAN Chinese subjects. METHODS: Seven very extensive metabolizers (VEM) and nine intermediate metabolizers ( IM) were enrolled from a Chinese population whose phenotype had been previously assessed with a dextromethorphan metabolic phenotyp-ing. The blood samples (0 - 15 h) were taken after oral administration of a single dose (400 mg) of rac-Pro hydrochloride. Enantiomeric concentrations of propafenone in plasma were measured by a reverse-phase HPLC with precolumn derivatization. RESULTS: S-Pro was less metabolized and had higher plasma concentrations than R-Pro in both CYP2D6 phenotypes. Besides, the T1/2 of R-Pro was longer than that of S-Pro in IM, but not in VEM. However, there were significant differences in the metabolism of Pro enantiomers between VEM and IM. The Cmax and AUC of both isomers in the IM group were higher than those in the VEM group (P < 0.01). The Cl of Pro enantiomers in IM group was only about half of that in VEM group [(67 ±17) vs (133±28) L·h-1 for S-Pro, (90±24) vs (200±87) L·h-1 for R-Pro, P<0.01]. The S/R ratios of T1/2, Tmax, Cmax, Cl, and AUC were not significantly different ( P > 0.05). CONCLUSION: CYP2D6 phenotype determines the pharmacokinetic variability of propafenone enantiomers and existence of IM may be relevant to diminished capacity of CYP2D6 enzyme in Chinese subjects.

关 键 词：普罗帕酮 立体异构 药物动力学 CYP2D6 表型 

分 类 号：R972.2[医药卫生—药品]