Arya Vikram, Ma Joseph D, Kvitne Kine Eide
Division of Infectious Disease Pharmacology, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA.
Pharmaceutics. 2024 Jun 25;16(7):855. doi: 10.3390/pharmaceutics16070855.
The evaluation of transporter-mediated drug-drug interactions (DDIs) during drug development and post-approval contributes to benefit-risk assessment and helps formulate clinical management strategies. The use of endogenous biomarkers, which are substrates of clinically relevant uptake and efflux transporters, to assess the transporter inhibitory potential of a drug has received widespread attention. Endogenous biomarkers, such as coproporphyrin (CP) I and III, have increased mechanistic understanding of complex DDIs. Other endogenous biomarkers are under evaluation, including, but not limited to, sulfated bile acids and 4-pyridoxic acid (PDA). The role of endogenous biomarkers has expanded beyond facilitating assessment of transporter-mediated DDIs and they have also been used to understand alterations in transporter activity in the setting of organ dysfunction and various disease states. We envision that endogenous biomarker-informed approaches will not only help to formulate a prudent and informed DDI assessment strategy but also facilitate quantitative predictions of changes in drug exposures in specific populations.
在药物研发和获批后阶段对转运体介导的药物相互作用（DDIs）进行评估，有助于进行获益-风险评估，并有助于制定临床管理策略。使用内源性生物标志物（它们是临床相关摄取和外排转运体的底物）来评估药物的转运体抑制潜力已受到广泛关注。内源性生物标志物，如粪卟啉（CP）I和III，增加了对复杂药物相互作用的机制理解。其他内源性生物标志物正在评估中，包括但不限于硫酸化胆汁酸和4-吡哆酸（PDA）。内源性生物标志物的作用已扩展到促进对转运体介导的药物相互作用的评估之外，它们还被用于了解器官功能障碍和各种疾病状态下转运体活性的变化。我们设想，基于内源性生物标志物的方法不仅将有助于制定谨慎且明智的药物相互作用评估策略，还将促进对特定人群中药物暴露变化的定量预测。
