Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India.
Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India.
Drug Metab Rev. 2021 Aug;53(3):285-320. doi: 10.1080/03602532.2021.1928687. Epub 2021 Jun 2.
Drug-drug interactions mediated by transporters are a serious clinical concern hence a tremendous amount of work has been done on the characterization of the transporter-mediated proteins in humans and animals. The underlying mechanism for the transporter-mediated drug-drug interaction is the induction or inhibition of the transporter which is involved in the cellular uptake and efflux of drugs. Transporter of the brain, liver, kidney, and intestine are major determinants that alter the absorption, distribution, metabolism, excretion profile of drugs, and considerably influence the pharmacokinetic profile of drugs. As a consequence, transporter proteins may affect the therapeutic activity and safety of drugs. However, mounting evidence suggests that many drugs change the activity and/or expression of the transporter protein. Accordingly, evaluation of drug interaction during the drug development process is an integral part of risk assessment and regulatory requirements. Therefore, this review will highlight the clinical significance of the transporter, their role in disease, possible cause underlying the drug-drug interactions using analytical tools, and update on the regulatory requirement. The recent approaches which emphasize the advancement in the discovery of drug-drug interactions are also highlighted in this review. Besides, we discuss several endogenous biomarkers that have shown to act as substrates for many transporters, which could be potent determinants to find the drug-drug interactions mediated by transporters. Transporter-mediated drug-drug interactions are taken into consideration in the drug approval process therefore we also provided the extrapolated decision trees from to , which may trigger the follow-up to clinical studies.
药物-药物相互作用通过转运蛋白介导是一个严重的临床问题，因此，人们在人类和动物中对转运蛋白介导的药物相互作用进行了大量的研究。转运蛋白介导的药物相互作用的潜在机制是转运蛋白的诱导或抑制，这涉及药物的细胞摄取和外排。脑、肝、肾和肠的转运蛋白是改变药物吸收、分布、代谢和排泄特征的主要决定因素，极大地影响了药物的药代动力学特征。因此，转运蛋白可能会影响药物的治疗活性和安全性。然而，越来越多的证据表明，许多药物会改变转运蛋白的活性和/或表达。因此，在药物开发过程中评估药物相互作用是风险评估和监管要求的一个组成部分。因此，本综述将重点介绍转运蛋白的临床意义、它们在疾病中的作用、使用分析工具的药物-药物相互作用的潜在原因，以及更新的监管要求。本综述还强调了最近强调发现药物-药物相互作用的新方法。此外，我们讨论了几种内源性生物标志物，这些标志物已被证明是许多转运体的底物，它们可能是发现转运体介导的药物-药物相互作用的有力决定因素。在药物批准过程中考虑了转运体介导的药物-药物相互作用，因此我们还提供了从到的外推决策树，这可能会引发对临床研究的跟进。
