Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tübingen, Auerbachstrasse 112, 70376 Stuttgart, Germany.
Expert Opin Drug Metab Toxicol. 2012 Dec;8(12):1565-77. doi: 10.1517/17425255.2012.722996. Epub 2012 Sep 13.
Antimicrobial drugs are essential in the treatment of infectious diseases. A better understanding of transport processes involved in drug disposition will improve the predictability of drug-drug interactions with consequences for drug response. Multidrug And Toxin Extrusion (MATE; SLC47A) proteins are efflux transporters mediating the excretion of several antimicrobial drugs as well as other organic compounds into bile and urine, thereby contributing to drug disposition.
This review summarizes current knowledge of the structural and molecular features of human MATE transporters including their functional role in drug transport with a specific focus on antimicrobial drugs. The PubMed database was searched using the terms "MATE1," "MATE-2K," "MATE2," "SLC47A1," "SLC47A2," and "toxin extrusion protein" (up to June 2012).
MATE proteins have been recognized as important transporters mediating the final excretion step of cationic drugs into bile and urine. These include the antiviral drugs acyclovir, amprenavir, and ganciclovir, the antibiotics cephalexin, cephradine and levofloxacin, as well as the antimalarial agents chloroquine and quinine. It is therefore important to enhance our understanding of the role of MATEs in drug extrusion with particular emphasis on the functional consequences of genetic variants on disposition of these antimicrobial drugs.
抗生素在传染病的治疗中至关重要。深入了解药物处置过程中的转运机制,将提高药物相互作用的预测能力,从而影响药物的反应。多药和毒素外排(MATE;SLC47A)蛋白是外排转运蛋白,可将多种抗生素以及其他有机化合物分泌到胆汁和尿液中,从而影响药物的处置。
本综述总结了人源 MATE 转运蛋白的结构和分子特征的最新知识,包括其在药物转运中的功能作用,特别是针对抗生素。使用术语“MATE1”、“MATE-2K”、“MATE2”、“SLC47A1”、“SLC47A2”和“毒素外排蛋白”(截至 2012 年 6 月)在 PubMed 数据库中进行搜索。
MATE 蛋白已被认为是介导阳离子药物最终排入胆汁和尿液的重要转运蛋白。其中包括抗病毒药物阿昔洛韦、安普那韦和更昔洛韦、抗生素头孢氨苄、头孢拉定和左氧氟沙星,以及抗疟药物氯喹和奎宁。因此,重要的是要增强我们对 MATE 在药物外排中的作用的理解,特别强调遗传变异对这些抗生素药物处置的功能后果。