普罗帕酮的对映体选择性药代动力学研究  

STEREOSELECTIVE PHARMACOKINETIC STUDIES ON THE PROPAFENONE ENANTIOMERS

作　　者：钟大放[1] 王亚芹[1] 王爱民[1] 

机构地区：[1]沈阳药科大学药物代谢与药物动力学实验室

出　　处：《中国临床药理学杂志》1997年第2期82-87,共6页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金

摘　　要：本文研究了１０名中国汉族健康受试者单剂量口服３００ｍｇ盐酸普罗帕酮后药代动力学的对映体选择性。结果表明，（Ｓ）－（＋）－与（Ｒ）－（－）－普罗帕酮的Ｃｍａｘ比值为１．６１±０．１５，ＡＵＣ的相应比值为１．４３±０．１０，具有β受体阻断作用的（Ｓ）－对映体血浆浓度始终高于（Ｒ）－对映体；在普罗帕酮代谢快慢与代谢的对映体选择性之间未观察到相关性。同时发现，受试者虽均属普罗帕酮强代谢型，但个体间ＡＵＣ值相差达１２．１倍；受试者血浆中普罗帕酮和活性代谢物５－羟基普罗帕酮的浓度呈正相关，ｒ＝０．８０４；与白种人强代谢型受试者的结果相比，中国受试者的普罗帕酮ＡＵＣ平均值较高（Ｐ＜０．０１），且个体差异较大（Ｐ＜０．０１）。After a single oral dose of 300 mg (±)-propanenone hydrochloride by 10 healthy Han-Chinese volunteers, enantioselective pharmacokinetics were investigated. It was found that the Cmax ratio of (S)-(+)- to (R)-(-)-propafenone was 1.61±0.15, and the corresponding AUC ratio was 1.43±0.10. Plasma concentrations of the more potent β-adrenergic blocker (S)-enantiomer were always greater than those of (R)-enantiomer. No correlation was observed between the rate of propafenone disposition and its metabolic stereoselectivity. Furthermore, it was found that the interindividual AUC differences were as high as to 12.1 times, although the volunteers all belonged to extensive metabolizers. The AUCs of propafenone were demonstrated to be somewhat proportional to that of its active metabolite 5-hydroxypropafenone with r= 0.804. Comparing with the results of the Caucasian extensive metabolizers given the identical dosage, the AUC mean value of propafenone in the Chinese subjects was greater (P< 0.01), and so was the inter-individual AUC variability (P< 0.01).

关 键 词：普罗帕酮 对映体 药代动力学 

分 类 号：R972.2[医药卫生—药品]