Tamsulosin alters the pharmacokinetics of metformin via inhibition of renal multidrug and toxin extrusion protein 1 and organic cation transporter 2 in rats

Among the endocrine and metabolic disorders, type-2 diabetes mellitus (T2DM) and benign prostatic hyperplasia (BPH) are common progressive diseases related to aging. Metformin and tamsulosin as the first-choice drug for patients with T2DM and BPH, respectively, are often co-administered to male patients with T2DM and BPH. However, whether concomitantly administering metformin and tamsulosin leads to drug-drug interactions (DDIs) remains unclear. This study aimed to evaluate the effect of tamsulosin on the pharmacokinetics of metformin and explore the relevant underlying mechanism. The plasma, urine, and tissue concentrations of metformin were analyzed using HPLC, and metformin cell uptake was analyzed using LC-MS/MS. In addition, western blotting was used to investigate the expression of Oct1, Oct2, and Mate1. As demonstrated by comparison with metformin alone, tamsulosin significantly increased the area under concentration-time curves (AUC