Institute of Experimental & Clinical Pharmacology & Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054 Erlangen, Germany.
Pharmacogenomics. 2011 Jul;12(7):1017-37. doi: 10.2217/pgs.11.44.
Drug-drug interactions are a serious clinical issue. An important mechanism underlying drug-drug interactions is induction or inhibition of drug transporters that mediate the cellular uptake and efflux of xenobiotics. Especially drug transporters of the small intestine, liver and kidney are major determinants of the pharmacokinetic profile of drugs. Transporter-mediated drug-drug interactions in these three organs can considerably influence the pharmacokinetics and clinical effects of drugs. In this article, we focus on probe drugs lacking significant metabolism to highlight mechanisms of interactions of selected intestinal, hepatic and renal drug transporters (e.g., organic anion transporting polypeptide [OATP] 1A2, OATP2B1, OATP1B1, OATP1B3, P-gp, organic anion transporter [OAT] 1, OAT3, breast cancer resistance protein [BCRP], organic cation transporter [OCT] 2 and multidrug and toxin extrusion protein [MATE] 1). Genotype-dependent drug-drug interactions are also discussed.
药物相互作用是一个严重的临床问题。药物相互作用的一个重要机制是诱导或抑制介导外源性物质细胞摄取和外排的药物转运体。特别是小肠、肝脏和肾脏的药物转运体是药物药代动力学特征的主要决定因素。这三个器官中的转运体介导的药物相互作用会极大地影响药物的药代动力学和临床效果。在本文中，我们重点关注缺乏明显代谢的探针药物，以突出选定的肠、肝和肾药物转运体（如有机阴离子转运多肽 [OATP] 1A2、OATP2B1、OATP1B1、OATP1B3、P-糖蛋白、有机阴离子转运体 [OAT] 1、OAT3、乳腺癌耐药蛋白 [BCRP]、有机阳离子转运体 [OCT] 2 和多药和毒素外排蛋白 [MATE] 1）的相互作用机制。还讨论了基因型依赖性药物相互作用。
