Quantitative Drug Disposition, GlaxoSmithKline plc, King of Prussia, Pennsylvania, USA.
Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Inc, Kenilworth, New Jersey, USA.
Clin Pharmacol Ther. 2018 Nov;104(5):781-784. doi: 10.1002/cpt.1082. Epub 2018 May 15.
Metformin drug-drug interaction (DDI) studies are conducted during development of drugs that inhibit organic cation transporters and/or multidrug and toxin extrusion proteins (OCTs/MATEs). Monitoring solely changes in systemic exposure, the typical DDI study endpoint appears inadequate for metformin, which is metabolically stable, has poor passive membrane permeability, and undergoes transporter-mediated tissue distribution and clearance. Evaluation of renal clearance, antihyperglycemic effects, and potentially lactate as an exploratory safety marker, can support rational metformin dose adjustment. The proposed DDI study design aims to adequately inform metformin dosing during comedication.
二甲双胍药物-药物相互作用（DDI）研究在开发抑制有机阳离子转运体和/或多药和毒素外排蛋白（OCTs/MATEs）的药物期间进行。仅监测系统暴露的变化，对于代谢稳定、被动膜通透性差、并通过转运体介导组织分布和清除的二甲双胍来说，典型的 DDI 研究终点似乎不够充分。评估肾清除率、降血糖作用以及潜在的乳酸作为探索性安全标志物，可支持合理调整二甲双胍剂量。所提出的 DDI 研究设计旨在为合并用药期间的二甲双胍给药提供充分信息。
