[The drug-drug interaction mediated by efflux transporters and CYP450 enzymes].
[The drug-drug interaction mediated by efflux transporters and CYP450 enzymes].
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[外排转运蛋白和 CYP450 酶介导的药物相互作用]。
DOI：
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Ke
中科院分区：
文献类型：
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作者：
Chong Wang;Ke
多药治疗方案及相应的药物相互作用会导致许多不良反应和治疗失败。药物外排转运蛋白：P-糖蛋白（P-gp）、多药耐药相关蛋白（MRP）和乳腺癌耐药蛋白（BCRP）与代谢酶（细胞色素P450，CYP 450）的协同作用是这种相互作用的主要因素。近年来，大量研究表明P-gp在其底物的氧化代谢中发挥作用，这些底物也是CYP 3A 4的底物。P-gp和CYP 3A的联合作用可以在一定程度上解释许多这些双重底物的低口服生物利用度。P-gp与外排转运蛋白（MRP和BCRP）具有重叠的底物特异性，沿着在药物处置中起关键作用。MRP或BCRP与CYP 3A之间的关系与P-gp与CYP 3A之间的关系相似。本文综述了外排转运蛋白的分类、主要代谢酶CYP 3A、外排转运蛋白与CYP 450相互作用的临床意义以及体外研究进展。
Multidrug regimens and corresponding drug interactions cause many adverse reactions and treatment failures. Drug efflux transporters: P-glycoprotein (P-gp), multidrug resistance associated protein (MRP) and breast cancer resistance protein (BCRP) in conjunction with metabolizing enzymes (cytochrome P450, CYP450) are major factors in such interaction. In recent years, a large number of studies have shown that P-gp plays a role in the oxidative metabolism of its substrates that are also substrates of CYP3A4. Combined actions of P-gp and CYP3A could account in some part for the low oral bioavailability determined for many of these dual substrates. P-gp along with efflux transporters (MRP and BCRP) having overlapping substrate specificity plays critical role in drug disposition. The relationship between MRP or BCRP and CYP3A is similar to that between P-gp and CYP3A. In this paper, we summarize the classification of efflux transporters, the main metabolizing enzymes CYP3A, clinical significance interactions mediated by efflux transporters and CYP450 enzymes and in vitro studies.