Clinical aspects of the MDRI (ABCB1) gene polymorphism

被引:144
作者
Eichelbaum, M
Fromm, MF
Schwab, M
机构
[1] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany
[2] Univ Tubingen Hosp, Div Clin Pharmacol, D-72076 Tubingen, Germany
关键词
MDR1; P-glycoprotein; polymorphism; drug treatment;
D O I
10.1097/00007691-200404000-00017
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Transporter proteins, in particular P-glycoprotein (Pgp), are important determinants in absorption, tissue targeting, and elimination of drugs. In addition to physiological and environmental factors, its expression and function are modified by genetic polymorphisms of the MDR1 gene. So far, several MDR1 SNPs have been identified, and mutations at positions 2677 and 3435 were associated with alteration of Pgp expression and/or function. In contrast to drug-metabolizing enzymes (eg, CYP2D6), for which loss of function mutations or gene amplification manifests as distinct phenotypes in the population, the impact of MDR1 polymorphisms on pharmacokinetics and pharmacodynamics of Pgp substrates is moderate. Clinical studies on the effects of the C3435T polymorphism and drug treatment with cardiac glycosides, the immunosuppressants cyclosporine and tacrolimus, HIV protease inhibitors, and tricyclic antidepressants are discussed.
引用
收藏
页码:180 / 185
页数:6
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