Drug transporters determine plasma and tissue exposure of a broad variety of drugs and play a critical role in drug-drug interaction （DDI）. In the present study, we aimed to investigate the effects of carvedilol on pharmacokinetics of metformin as well as the mechanism of their interaction. Results showed that plasma concentration of metformin was not significantly altered after single or 7-day co-administration of carvedilol, and the urinary excretion of metformin was also not influenced by carvedilol. However, the concentration of metformJn in the liver and kidney was markedly elevated. Similarly, carvedilol did not affect the renal elimination of metformin, but increased renal concentration in isolated kidney perfusion. On the other hand, carvedilol treatment did not affect the expressions of rOCTs and rMATE 1 in the liver and kidney of rats. After long-term co-administration, there were no differences in lactic acid （LCA）, uric acid （URIC） and creatinine （CREA） levels between two groups. These results indicated that carvedilol increased hepatic and renal distribution of metformin, resulting in local drug interaction.
