PDF(Pubmed)
Abstract：
Membrane transporters play an important role in the absorption, distribution, metabolism, and excretion of xenobiotic substrates, as well as endogenous compounds. The evaluation of transporter-mediated drug-drug interactions (DDIs) is an important consideration during the drug development process and can guide the safe use of polypharmacy regimens in clinical practice. In recent years, several endogenous substrates of drug transporters have been identified as potential biomarkers for predicting changes in drug transport function and the potential for DDIs associated with drug candidates in early phases of drug development. These biomarker-driven investigations have been applied in both preclinical and clinical studies and proposed as a predictive strategy that can be supplanted in order to conduct prospective DDIs trials. Here we provide an overview of this rapidly emerging field, with particular emphasis on endogenous biomarkers recently proposed for clinically relevant uptake transporters.
摘要：
膜转运体在吸收中起着重要作用,分布，新陈代谢，和外源性生物底物的排泄，以及内源性化合物。转运体介导的药物-药物相互作用（DDI）的评估是药物开发过程中的重要考虑因素，可以指导临床上安全使用多药方案。近年来,药物转运蛋白的几种内源性底物已被确定为潜在的生物标志物,可用于预测药物转运功能的变化以及药物开发早期候选药物的潜在DDI.这些生物标志物驱动的研究已被应用于临床前和临床研究，并被提出作为一种预测策略，可以取代以进行前瞻性DDI试验。在这里，我们概述了这个迅速出现的领域，特别强调最近提出的用于临床相关摄取转运蛋白的内源性生物标志物。
