转运体在药物经肝脏清除过程中的作用Roleoftransporters-药学学报.PDFVIP

药学学报 Acta Pharmaceutica Sinica 2012, 47 (5) : 565 572 ·565 · 转运体在药物经肝脏清除过程中的作用 高纯颖, 陈笑艳, 钟大放* ( 中国科学院上海药物研究所, 上海 201203) 摘要: 肝脏在药物的体内清除过程中具有重要作用, 它不仅是药物代谢的主要场所, 还控制着药物及其代 谢物的胆汁排泄过程。转运体是控制细胞内外物质传输的一类功能性膜蛋白, 其在肝脏有广泛表达, 并能对药物 进入肝细胞以及排泄至胆汁的过程进行调控, 因而, 对于肝脏清除过程具有重要作用。本文从肝脏中重要转运体 的分布、功能以及底物选择性出发, 对其在 物的肝脏清除中的作用、由其引起的药物 药物相互作用以及重要 转运体的 因多态性研究进行了综述。 关键词: 肝脏清除; 转运体; 药物 物相互作用 中图分类号: R969 文献标识码:A 文章编号: 05 13-4870 (2012) 05-0565-08 Role of transporters in hepatic drug disposition * GAO Chun-ying, CHEN Xiao-yan, ZHONG Da-fang (Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China) Abstract: Liver is regarded as one of the most important organs for drug clearance in the body, which mediates both the metabolism and biliary excretion of drugs. Transporters are a class of functional membrane proteins and control the movement of substances into or out of cells. Transporters, which are extensively expressed in the liver, play important roles in the drug hepatic disposition by regulating the uptake of drugs from blood into hepatocytes or the efflux of drugs and their metabolites into bile. In this review, the localization, functions and substrate selectivity of the maj or transporters in the liver will be summarized, and the impacts of these transporters on drug hepatic disposition, the potential drug-drug interactions as well as their genetic polymorphisms will