Metoprolol decreases the plasma exposure of metformin via the induction of liver, kidney and muscle uptake in rats

In this study, rats were treated with metformin alone or in combination with metoprolol. Plasma, urine and tissue concentrations of metformin were determinated by HPLC. Western blotting and real‐time qPCR were used to evaluate the expression of rOCTs and rMATE1. The results showed that, after single or 7‐day repeated administration, the plasma concentrations of metformin in the co‐administration group were significantly decreased compared to that in the metformin group. However, the parameter V/F of metformin in the co‐administration group was markedly increased compared to that in the metformin group. The hepatic, renal and muscular Kp of metformin were markedly elevated after co‐administration with metoprolol. Consistently, metformin uptake in rat kidney slices was significantly induced by metoprolol. In addition, multiple administration of metoprolol significantly reduced the expression of rMATE1 in rat kidney as well as the urinary excretion of metformin. Importantly, after long‐term administration, lactic acid and uric acid levels in the co‐administration group were increased by 25% and 26%, respectively, compared to that in the metformin group. These results indicate that metoprolol can decrease the plasma concentration of metformin via the induction of hepatic, renal and muscular uptake, and long‐term co‐administration of metformin and metoprolol can cause elevated lactic acid and uric acid levels.
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: Original Paper Source Type: research