Abstract：
Comprehensive characterization of transporter mediated drug-drug interactions (DDIs) is important to formulate clinical management strategies and ensure the safe and effective use of concomitantly administered drugs. The potential of a drug to inhibit transporters is predicted by comparing the ratio of the relevant concentration (depending on the transporter) and the half maximum inhibitory concentration to a predefined \"cutoff\" value. If the ratio is greater than the cutoff value, modeling approaches such as physiologically based pharmacokinetic modeling or a clinical DDI trial may be recommended. Because false-positive (in vitro data suggest the potential for a DDI, whereas no significant DDI is observed in vivo) and false-negative (in vitro data does not suggest the potential for a DDI, whereas significant DDI is observed in vivo) outcomes have been observed, there is interest in exploring additional approaches to facilitate prediction of transporter-mediated DDIs. The idea of assessing changes in the concentration of endogenous biomarkers (which are substrates of clinically relevant transporters) to gain insight on the potential for a drug to inhibit transporter activity has received widespread attention. This brief report describes how endogenous biomarkers may help to expand the DDI assessment toolkit, highlights some current knowledge gaps, and outlines a conceptual framework that may complement the current paradigm of predicting the potential for transporter-mediated DDIs.
摘要：
转运体介导的药物-药物相互作用（DDI）的综合表征对于制定临床管理策略和确保伴随给药的安全有效使用非常重要。通过将相关浓度（取决于转运蛋白）和半最大抑制浓度的比率与预定义的“截止”值进行比较，可以预测药物抑制转运蛋白的潜力。如果该比率大于截止值，可推荐采用基于生理的药代动力学建模或临床DDI试验等建模方法.因为假阳性(体外数据表明DDI的潜力，而在体内没有观察到显著的DDI)和假阴性(体外数据并不表明DDI的潜力，而在体内观察到显著的DDI)结果已经观察到，有兴趣探索其他方法来促进转运蛋白介导的DDI的预测。评估内源性生物标志物(其是临床相关转运蛋白的底物)的浓度变化以获得对药物抑制转运蛋白活性的潜力的洞察的想法已经受到广泛关注。这份简短报告描述了内源性生物标志物如何帮助扩展DDI评估工具包，突出了当前的一些知识差距，并概述了一个概念框架，可以补充预测转运蛋白介导的DDI潜力的当前范式。
