Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Dig Liver Dis. 2013 Sep 30;45 Suppl 5:S343-8. doi: 10.1016/j.dld.2013.07.008.
With the licensing of the direct acting antivirals telaprevir and boceprevir the topic of drug-drug interactions has come to the forefront. These first generation hepatitis C virus protease inhibitors are metabolized by and inhibit the key drug metabolizing enzyme CYP3A4, which means that knowledge of drug-drug interactions has become an essential component of the evaluation of a patient starting triple therapy. The number of potential co-medications means that many drugs will be used in hepatitis C virus patients where there are no pharmacokinetic study data. Here we have to use the data that are available and seek to extrapolate to unstudied drugs using key principles of clinical pharmacology (disposition characteristics, concentration-effect relationships, therapeutic window) in order to give some guidance for management of patients. This is a rapidly moving area in hepatitis C therapy, both in terms of understanding the drug interaction profile of telaprevir and boceprevir, interaction mechanisms that sometimes appear counterintuitive and that may involve enzymes other than CYP3A4 or transporters, but then seeking to understand the interaction potential of the next wave of drugs that will soon be with us.
随着直接作用抗病毒药物特拉普韦和博赛匹韦的许可，药物相互作用的话题成为了焦点。这些第一代丙型肝炎病毒蛋白酶抑制剂通过代谢并抑制关键的药物代谢酶 CYP3A4 来代谢，这意味着药物相互作用的知识已成为评估开始三联疗法的患者的重要组成部分。潜在的合并用药数量意味着在丙型肝炎病毒患者中会使用许多没有药代动力学研究数据的药物。在这里，我们必须使用现有的数据，并寻求使用临床药理学的关键原则（处置特征、浓度-效应关系、治疗窗口）来推断未研究的药物，以便为患者的管理提供一些指导。这是丙型肝炎治疗中一个快速发展的领域，涉及到对特拉普韦和博赛匹韦的药物相互作用谱的理解、有时似乎违反直觉的相互作用机制，这些机制可能涉及除 CYP3A4 以外的其他酶或转运体，然后还要了解即将面世的下一波药物的相互作用潜力。
