The conduct of in vitro and in vivo drug-drug interaction studies: A Pharmaceutical Research and Manufacturers of America (PhRMA) perspective
The conduct of in vitro and in vivo drug-drug interaction studies: A Pharmaceutical Research and Manufacturers of America (PhRMA) perspective
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DOI：
10.1124/dmd.31.7.815
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发表时间：
2003-07-01
影响因子：
3.9
通讯作者：
Wrighton, SA
中科院分区：
文献类型：
--
作者：
Bjornsson, TD;Callaghan, JT;Wrighton, SA
目前的监管指南没有针对体外和体内药物相互作用研究的具体研究设计。监管机构和行业发起人都希望统一方法，以便更好地评估不同研究和药物发现的重要性。对于细胞色素P450 （P450）探针底物、抑制剂和诱导剂的标准化以及分类系统的发展，以改善与卫生保健提供者和患者的风险沟通，也有越来越多的共识。虽然现有的指南主要涵盖p450介导的药物相互作用，但其他机制（如转运蛋白）的重要性最近已被认识到，也应该加以解决。本文由美国药物研究和制造商协会（PhRMA）药物代谢和临床药理学技术工作组编写，代表了当前的行业立场。目的是为体外和体内药代动力学药物-药物相互作用研究定义一个最小的最佳实践，以开发为目标（不支持发现），并定义一个可由监管机构在化合物注册档案中期望的数据包。
Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers.