The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans

被引:221
作者
Fromm, MF [1 ]
机构
[1] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany
关键词
drug transport; drug efflux; SNP; pharmacokinetics; digoxin; HIV; intestine; placenta; blood-brain barrier;
D O I
10.1016/S0169-409X(02)00064-9
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The MDR1 (ABCB1) gene product P-glycoprotein is a membrane protein, which functions as an ATP-dependent exporter of xenobiotics from cells. Its importance was first recognized because of its role in the development of multidrug resistance (MDR) of cultured tumor cells against various anticancer agents. It is now, however, well established that this transporter is not only expressed in tumor cells, but also in normal tissues with excretory function (intestine, liver, kidney). Since P-glycoprotein has a very broad substrate specificity, it determines disposition of a broad variety of drugs. Moreover, induction and inhibition of P-glycoprotein are new mechanisms for drug interactions in humans. Very recently, systematic screens of the MDR1 gene have identified multiple single nucleotide polymorphisms. Some of those appear to be associated with altered transporter function and expression. This review discusses the currently available data on the influence of MDR1 polymorphisms on P-glycoprotein tissue expression, drug disposition, treatment outcome and disease risk. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:1295 / 1310
页数:16
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