Department of Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Molecules. 2023 Jul 6;28(13):5252. doi: 10.3390/molecules28135252.
The kidney is critical in the human body's excretion of drugs and their metabolites. Renal transporters participate in actively secreting substances from the proximal tubular cells and reabsorbing them in the distal renal tubules. They can affect the clearance rates (CLr) of drugs and their metabolites, eventually influence the clinical efficiency and side effects of drugs, and may produce drug-drug interactions (DDIs) of clinical significance. Renal transporters and renal transporter-mediated DDIs have also been studied by many researchers. In this article, the main types of in vitro research models used for the study of renal transporter-mediated DDIs are membrane-based assays, cell-based assays, and the renal slice uptake model. In vivo research models include animal experiments, gene knockout animal models, positron emission tomography (PET) technology, and studies on human beings. In addition, in vitro-in vivo extrapolation (IVIVE), ex vivo kidney perfusion (EVKP) models, and, more recently, biomarker methods and in silico models are included. This article reviews the traditional research methods of renal transporter-mediated DDIs, updates the recent progress in the development of the methods, and then classifies and summarizes the advantages and disadvantages of each method. Through the sorting work conducted in this paper, it will be convenient for researchers at different learning stages to choose the best method for their own research based on their own subject's situation when they are going to study DDIs mediated by renal transporters.
肾脏在人体排出药物及其代谢物方面起着关键作用。肾脏转运体参与将物质从近端肾小管细胞主动分泌，并在远端肾小管中重吸收。它们可以影响药物及其代谢物的清除率（CLr），最终影响药物的临床疗效和副作用，并可能产生具有临床意义的药物-药物相互作用（DDIs）。许多研究人员也研究了肾脏转运体和肾脏转运体介导的 DDIs。在本文中，研究肾脏转运体介导的 DDIs 的主要体外研究模型包括基于膜的测定、基于细胞的测定和肾切片摄取模型。体内研究模型包括动物实验、基因敲除动物模型、正电子发射断层扫描（PET）技术和对人类的研究。此外，还包括体外-体内外推（IVIVE）、离体肾脏灌注（EVKP）模型，以及最近的生物标志物方法和计算模型。本文回顾了肾脏转运体介导的 DDIs 的传统研究方法，更新了方法的最新进展，然后对每种方法的优缺点进行分类和总结。通过本文的分类工作，不同学习阶段的研究人员在研究肾脏转运体介导的 DDIs 时，可以根据自己的课题情况，选择最适合自己研究的方法。
