Department of Clinical Pharmacology, Clinical Research, Pfizer Japan Inc., 3-22-7, Yoyogi, Shibuya-ku, Tokyo 151-8589, Japan.
Pharmacogenomics. 2013 Nov;14(14):1745-64. doi: 10.2217/pgs.13.171.
Drug transporters, together with drug metabolic enzymes, are major determinants of drug disposition and are known to alter the response to many commonly used drugs. Substantial frequency differences for known variants exist across geographic regions for certain drug transporters. To deliver efficacious medicine with the right dose for each patient, it is important to understand the contribution of genetic variants for drug transporters. Recently, mutual pharmacokinetic data usage among Asian regions, which are thought to be relatively similar in their own genetic background, is expected to accelerate new drug applications and reduce developmental costs. Polymorphisms of drug transporters could be key factors to be considered in implementing multiethnic global clinical trials. This review addresses the current knowledge on genetic variations of major drug transporters affecting drug disposition, efficacy and toxicity, focusing on the east Asian populations, and provides insights into future directions for precision medicine and drug development in east Asia.
药物转运体与药物代谢酶一起,是药物处置的主要决定因素,已知它们会改变许多常用药物的反应。某些药物转运体在不同地理区域的已知变体存在显著的频率差异。为了为每个患者提供有效且剂量合适的药物,了解药物转运体的遗传变异体的贡献非常重要。最近,亚洲地区之间预期将加速新药申请并降低开发成本的相互药代动力学数据使用,这些地区在遗传背景上被认为相对相似。药物转运体的多态性可能是实施多民族全球临床试验时需要考虑的关键因素。这篇综述讨论了影响药物处置、疗效和毒性的主要药物转运体的遗传变异的最新知识,重点关注东亚人群,并为东亚精准医学和药物开发的未来方向提供了见解。