College of Pharmacy, Dongguk University, Seoul 100-715, Korea.
Arch Pharm Res. 2011 Nov;34(11):1865-77. doi: 10.1007/s12272-011-1107-y. Epub 2011 Dec 3.
Over the past few decades, a tremendous amount of work has been done on the molecular characterization of transport proteins in animals and humans, leading to a better understanding of the physiological roles of a number of transport proteins. Furthermore, there is increasing preclinical and clinical evidence to support the importance of transport proteins in the pharmacokinetics and toxicokinetics of a wide variety of structurally diverse drugs. As a consequence, the degree of expression and functionality of transport proteins may directly affect the therapeutic effectiveness, safety and target specificity of drugs. Recently, there has also been increased awareness about potential drug-drug, drug-herb and drug-food interactions involving transporters. Traditionally, a change in metabolic clearance of a drug, particularly via cytochrome P450-mediated metabolism, has been considered the cause of many clinically important drug interactions. However, increasing evidence suggests that some drug interactions result from changes in the activity and/or expression of drug transporters. Accordingly, assessment of the clinical relevance of transporter-mediated drug interactions has become a regulatory issue during the drug approval process and also the evaluation of drug interaction potential has become an integral part of risk assessment during drug development processes. Therefore, this review will highlight the role of some selected drug transporters in drug interactions, as well as their clinical implication.
在过去的几十年中，人们对动物和人类的转运蛋白的分子特征进行了大量的研究，从而更好地了解了许多转运蛋白的生理作用。此外，越来越多的临床前和临床证据支持转运蛋白在广泛的结构多样的药物的药代动力学和毒代动力学中的重要性。因此，转运蛋白的表达和功能程度可能直接影响药物的治疗效果、安全性和靶标特异性。最近，人们也越来越意识到涉及转运蛋白的药物-药物、药物-草药和药物-食物相互作用的潜在可能性。传统上，药物代谢清除率的变化，特别是通过细胞色素 P450 介导的代谢，被认为是许多临床上重要的药物相互作用的原因。然而，越来越多的证据表明，一些药物相互作用是由于药物转运蛋白的活性和/或表达的变化引起的。因此，评估转运体介导的药物相互作用的临床相关性已成为药物审批过程中的一个监管问题，同时药物相互作用潜力的评估也已成为药物开发过程中风险评估的一个组成部分。因此，这篇综述将重点介绍一些选定的药物转运体在药物相互作用中的作用及其临床意义。
