多态变异对药物转运体活性影响及其临床意义  

Effect of genetic polymorphism on the activity of drug transporters and its clinical significance

作　　者：张海霞[1] 王连生[1] 

机构地区：[1]中南大学临床药理研究所,长沙410008

出　　处：《中南大学学报（医学版）》2008年第8期765-768,F0003,共5页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(30200346)~~

摘　　要：药物转运是药物反应个体差异及药物相互作用的重要环节。近年来,随着物质转运研究的深入,转运蛋白超家族成员正在不断增加。在已发现和命名的转运蛋白中,与药物转运有关的主要蛋白有ATP依赖性泵出转运体MDR1、有机阴离子转运蛋白(OATP)。MDR1在胃肠道、肝脏和肾脏等组织广泛分布,影响药物的吸收、分布以及分泌排泄。MDR1基因的多态性影响其表达和功能,改变底物药物体内过程。有机阴离子转运蛋白在肝脏等组织特异表达,调节药物的分泌排出,其遗传多态性是相关药物异常反应的重要原因。Drug transport is an important source of inter-individual variations in drug responses and is also a common site where drug-drug interactions happen. In recent years, more and more novel identified transporters have been added into the transporter super family, and this trend will continue in the future, Among the transporter members of this family, ATP-dependent efflux transporter P-glycoprotein （ MDR1 ） and organic anion transporters （ OATP ） are the most important proteins involved in drug transport. MDR1 is the most well known transporter, Widely distributed in tissues such as the gastrointestinal tract, liver, kidney and so on, MDR1 plays an important role in drug absorption, distribution and excretion, Its functional genetic polymorphisms have significantly changed the pharmacokinetics of its substrate drugs, which has important clinical implications. OATP expressed in multiple tisues, and it mediated the drug excretion through the bile acid and kidney. Some genetic polymorphism of OATP genes is the cause of some abnormal drug responses,

关 键 词：多药耐药蛋白 有机阴离子转运体 遗传多态性 

分 类 号：R969[医药卫生—药理学]