Ho Richard H, Kim Richard B
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Clin Pharmacol Ther. 2005 Sep;78(3):260-77. doi: 10.1016/j.clpt.2005.05.011.
The efficacy of drug therapy results from the complex interplay of multiple processes that govern drug disposition and response. Most studies to date have focused on the contribution of drug-metabolizing enzymes to the drug disposition process. However, over the past decade, it has become increasingly apparent that carrier-mediated processes, or transporters, also play critical roles in the overall disposition of numerous drugs in clinical use. In addition to their roles in xenobiotic transport, drug transporters often mediate important physiologic functions via transport of endogenous substrates such as amino acids, bile acids, and hormones that are critical for maintenance of normal homeostasis. In this review we focus on the emerging field of transporter proteins in relation to the drug disposition process, with particular emphasis on clinical implications of transporters to drug-drug interactions and subsequent development of adverse effects, interindividual variability in drug response, and human disease.
药物治疗的疗效源于多个控制药物处置和反应过程之间复杂的相互作用。迄今为止，大多数研究都集中在药物代谢酶对药物处置过程的作用上。然而，在过去十年中，越来越明显的是，载体介导的过程，即转运体，在临床使用的众多药物的整体处置中也起着关键作用。除了在异源物质转运中的作用外，药物转运体还常常通过转运内源性底物（如对维持正常体内平衡至关重要的氨基酸、胆汁酸和激素）来介导重要的生理功能。在本综述中，我们重点关注转运蛋白与药物处置过程相关的新兴领域，特别强调转运体对药物相互作用及随后不良反应的发生、药物反应的个体间差异和人类疾病的临床意义。
