Bjornsson Thorir D, Callaghan John T, Einolf Heidi J, Fischer Volker, Gan Lawrence, Grimm Scott, Kao John, King S Peter, Miwa Gerald, Ni Lan, Kumar Gondi, McLeod James, Obach R Scott, Roberts Stanley, Roe Amy, Shah Anita, Snikeris Fred, Sullivan John T, Tweedie Donald, Vega Jose M, Walsh John, Wrighton Steven A
Wyeth, Collegeville, Pennsylvania, USA.
Drug Metab Dispos. 2003 Jul;31(7):815-32. doi: 10.1124/dmd.31.7.815.
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.
当前的监管指南未涉及体外和体内药物相互作用研究的具体研究设计。监管机构和行业赞助商普遍希望统一方法，以便更好地评估不同研究和药物中研究结果的重要性。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开发分类系统以改善向医疗保健提供者和患者传达风险的问题，也越来越达成共识。虽然现有指南主要涵盖P450介导的药物相互作用，但其他机制（如转运体）的重要性最近已得到认可，也应予以关注。本文由美国制药研究与制造商协会（PhRMA）药物代谢与临床药理学技术工作组编写，代表了当前行业立场。目的是为针对开发（而非发现支持）的体外和体内药代动力学药物相互作用研究定义一个最低限度的最佳实践，并定义监管机构在化合物注册档案中可能期望的数据包。
