UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Molecules. 2023 Nov 10;28(22):7532. doi: 10.3390/molecules28227532.
P-glycoprotein (P-gp) is a crucial membrane transporter situated on the cell's apical surface, being responsible for eliminating xenobiotics and endobiotics. P-gp modulators are compounds that can directly or indirectly affect this protein, leading to changes in its expression and function. These modulators can act as inhibitors, inducers, or activators, potentially causing drug-drug interactions (DDIs). This comprehensive review explores diverse models and techniques used to assess drug-induced P-gp modulation. We cover several approaches, including , , , and methods, with their respective strengths and limitations. Additionally, we explore the therapeutic implications of DDIs involving P-gp, with a special focus on the renal and intestinal elimination of P-gp substrates. This involves enhancing the removal of toxic substances from proximal tubular epithelial cells into the urine or increasing the transport of compounds from enterocytes into the intestinal lumen, thereby facilitating their excretion in the feces. A better understanding of these interactions, and of the distinct techniques applied for their study, will be of utmost importance for optimizing drug therapy, consequently minimizing drug-induced adverse and toxic effects.
P-糖蛋白（P-gp）是一种位于细胞顶表面的重要膜转运蛋白，负责消除外源性和内源性物质。P-糖蛋白调节剂是可以直接或间接影响这种蛋白质的化合物，导致其表达和功能发生变化。这些调节剂可以作为抑制剂、诱导剂或激活剂，可能导致药物相互作用（DDIs）。本综述全面探讨了用于评估药物诱导的 P-糖蛋白调节的多种模型和技术。我们涵盖了几种方法，包括细胞培养模型、体内模型、体外模型和基于分子的方法，以及它们各自的优缺点。此外，我们探讨了涉及 P-糖蛋白的药物相互作用的治疗意义，特别关注 P-糖蛋白底物的肾和肠消除。这涉及增强将有毒物质从近端肾小管上皮细胞中清除到尿液中，或增加化合物从肠细胞转运到肠腔中的能力，从而促进它们在粪便中的排泄。更好地理解这些相互作用，以及用于研究这些相互作用的不同技术，对于优化药物治疗、最大限度地减少药物引起的不良反应和毒性至关重要。
