Effect of Glipizide and Glibenclamide on the Pharmacokinetics of Losartan

OBJECTIVE To study the effect of glipizide and glibenclamide on the pharmacokinetics of losartan in rats. METHODS Fifteen rats were randomly divided into 3 groups(control group, glipizide group and glibenclamide group) and administrated orally with 0.5%CMC, 10 mg·kg^-1 glipizide and 10 mg·kg^-1 glibenclamide, respectively. The 5 mg·kg^-1 losartan potassium was administrated orally to the rats 0.5 h later and blood samples were collected via tail vein at different time point, which were further processed and analyzed for the concentration of losartan and E-3174 by HPLC. The pharmacokinetic parameters were calculated by DAS, followed by statistical analysis. RESULTS When co-administrated with glipizide, the AUC, MRT and C_max of losartan and E-3174 were significantly increased and the clearance of losartan was significantly decreased; when co-administrated with glibenclamide, only the T_max of losartan and MRT of E-3174 were altered. CONCLUSION Glipizide significantly affected the pharmacokinetics of losartan and its metabolite E-3174 in rats. In clinic, when these two drugs are co-administrated, drug adverse reaction of losartan induced by drug-drug interaction should be paid attention to.