药物转运体介导的药物-药物相互作用研究进展OA

Drug transporters are key membrane proteins that regulate the disposition of numerous drugs within the body,and transporter-mediated drug-drug interactions(DDIs)directly impact drug pharmacokinetics and clinical medication safety,representing a core component of evaluation in both drug development and clinical practice.Major global regulatory agencies have issued specific guide-lines to standardize the evaluation of DDIs risks involving key transporters.This review summarizes the current research landscape of transporter-mediated DDIs,with a focus on interpreting the differences in core requirements and regulatory expectations outlined in the guidelines of the three major regulatory authorities—the Food and Drug Administration(FDA),European Medicines Agency(EMA)and Phar-maceuticals and Medical Devices Agency(PMDA).The advances in the application of in vitro-in vivo extrapolation(IVIVE)strategies are outlined,major challenges to IVIVE are underscored,and risk man-agement strategies are recommended.Current challenges in this field include a poor understanding of inter-individual variability,inaccuracy in IVIVE,and a lack of data from special populations.Future research should focus on optimizing experimental models and predictive methodologies and advancing the understanding of metabolic-transport interplay in order to provide evidence for risk management in drug development and precision medication.