Drug Interaction of Metformin and Aspirin in Rabbits

메트포르민과 아스피린의 약물상호작용

The purpose of this study was to investigate the effect of aspirin (5, 10, 20 mg/kg) on the pharmacokinetics of metformin $(15\;mg/kg)$ in rabbits. The plasma concentration of metformin was decreased significantly (p<0.05) by co-administration of aspirin (10, 20 mg/kg) compared with control. Area under the plasma concentration-time curve (AUC) of metformin was decreased significantly (p<0.05) by co-administration of aspirin (10, 20mg/kg) compared with control. Relative bioavailability $(R.B\%)$ of metformin by co-administration was 79.3 (5 mg/kg), 57.5 (10 mg/kg) and 62.5 (20 mg/kg). Peak plasma concentration of metformin was significantly (p<0.05) decreased by co-administration of aspirin (10, 20 mg/kg) compared with control. The elimination rate constant $(K_{el})$ of metformin was increased by co-administration of aspirin (10, 20 mg/kg) compared with control. The terminal half-lifes $(t_{1/2})$ and mean resident time (MRT) of metformin by co-administration of aspirin (10, 20 mg/kg) were decreased significantly (p<0.05) compared with control. It is considered that the significantly decreased plasma concentration and AUC of metrormin is due to increase of elimination in urine acidified by co-administration of aspirin. The results suggest that the dosage of metformin should be adjusted when metformin is co-administered with aspirin in the clinical situation.