Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Building 51, Room 3188, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Toxicol Appl Pharmacol. 2010 Mar 1;243(2):134-45. doi: 10.1016/j.taap.2009.12.016. Epub 2010 Jan 4.
Pharmacokinetic drug interactions can lead to serious adverse events or decreased drug efficacy. The evaluation of a new molecular entity's (NME's) drug-drug interaction potential is an integral part of risk assessment during drug development and regulatory review. Alteration of activities of enzymes or transporters involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by concomitant drugs may alter drug exposure, which can impact response (safety or efficacy). The recent Food and Drug Administration (FDA) draft drug interaction guidance (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf) highlights the methodologies and criteria that may be used to guide drug interaction evaluation by industry and regulatory agencies and to construct informative labeling for health practitioner and patients. In addition, the Food and Drug Administration established a "Drug Development and Drug Interactions" website to provide up-to-date information regarding evaluation of drug interactions (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm). This review summarizes key elements in the FDA drug interaction guidance and new scientific developments that can guide the evaluation of drug-drug interactions during the drug development process.
药代动力学药物相互作用可导致严重的不良事件或降低药物疗效。评估新的分子实体（NME）的药物相互作用潜力是药物开发和监管审查期间风险评估的一个组成部分。伴随药物改变参与新的分子实体的吸收、分布、代谢或排泄的酶或转运体的活性可能会改变药物暴露，从而影响反应（安全性或疗效）。最近食品和药物管理局（FDA）的药物相互作用指导草案（http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf）强调了可能用于指导行业和监管机构进行药物相互作用评估以及为医疗保健提供者和患者构建信息性标签的方法和标准。此外，食品和药物管理局建立了一个“药物开发和药物相互作用”网站，提供有关药物相互作用评估的最新信息（http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm）。这篇综述总结了 FDA 药物相互作用指导中的关键要素和新的科学进展，这些可以指导药物开发过程中药物相互作用的评估。
