PDF(Pubmed)
Abstract：
Small molecule drugs are becoming increasingly used in the treatment of inflammatory bowel diseases (IBD). However, unlike monoclonal antibody drugs, which have few interactions with other medications, the pharmacokinetics of small molecule drugs are complex and may be influenced by a myriad of drug-drug interactions (DDI) as well as by patient characteristics and food intake. This review aims to provide a concise practical guide to small molecule drug interactions for the use of IBD physicians. It starts with a brief overview of the main metabolizing enzymes and transporters involved in drug interactions and the Food and Drug Administration\'s (FDA) approach to determining drug-interaction hazard thresholds. It is then followed by a more detailed review of the pharmacokinetics of five novel small molecules approved in IBD: Tofacitinib, Upadacitinib, Filgotinib, Ozanimod, and Etrasimod, including their known interactions and specific warnings. This review will also inform readers on challenges in determining the actual magnitude of interactions and their clinical relevance, including the arbitrary nature of some hazard thresholds, the inference of the impact on metabolizing enzymes and transporters from single-drug assays which may not reflect poly-pharmaceutical regimens, and other challenges in this field which the IBD physician needs to be cognizant of. In practice, before administering a small molecule drug, it is advisable to evaluate any potential interactions with other medications the patient is receiving. An increased awareness by health care professionals and patients, may reduce the possible risks associated with DDI of small molecule IBD drugs.
摘要：
小分子药物越来越多地用于治疗炎症性肠病（IBD）。然而,与单克隆抗体药物不同，与其他药物几乎没有相互作用，小分子药物的药代动力学是复杂的,可能受到无数药物-药物相互作用(DDI)以及患者特征和食物摄入的影响.本综述旨在为IBD医师使用小分子药物相互作用提供简明实用指南。首先简要概述了药物相互作用中涉及的主要代谢酶和转运蛋白，以及食品和药物管理局（FDA）确定药物相互作用危险阈值的方法。然后，对IBD中批准的四种新型小分子的药代动力学进行了更详细的回顾：Tofacitinib，Upadacitinib,Filgotinib,和Ozanimod,包括它们已知的相互作用和特定的警告。这篇评论还将告知读者在确定相互作用的实际程度及其临床相关性方面的挑战。包括一些危险阈值的任意性质，单药测定对代谢酶和转运蛋白的影响的推断可能不反映多药物治疗方案，以及IBD医生需要认识到的该领域的其他挑战。在实践中,在施用小分子药物之前，建议评估与患者正在接受的其他药物的任何潜在相互作用。提高卫生保健专业人员和患者的认识，可以降低小分子IBD药物与DDI相关的可能风险。
