BACKGROUND: The influence of losartan on the hypoglycemic effect of glimepiride was studied in normal and diabetic rats. METHOD: Losartan and glimepiride were studied at a dose of 4.5 and 0.09 mg/kg and in normal and diabetic rats, respectively. The blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours and analyzed for glucose levels using a glucometer. RESULTS: Glimepiride exhibited a maximum reduction of blood glucose levels at the 4th hour in normal and diabetic rats. The maximum hypoglycemic effect was observed at the 6th hour in normal rats treated with losartan. In normal rats, losartan did not have any significant effect on the hypoglycemic activity of glimepiride in either the single- or multiple-dose interaction study. In the case of diabetic rats, losartan did not have any significant effect on the hypoglycemic activity of glimepiride in the single-dose interaction study, but a significant change was observed in the multiple-dose study of diabetic rats. Hence, the interaction was found to be pharmacodynamic. CONCLUSIONS: The study indicates that chronic losartan pretreatment elevates the hypoglycemic effect of glimepiride by a possible rise in insulin sensitivity and improving insulin homeostasis or may be due to the inhibition of CYP2C9. The study also suggests that caution may be recommended concerning combined use of losartan and an oral hypoglycemic agent, glimepiride.
BACKGROUND: The influence of losartan on the hypoglycemic effect of glimepiride was studied in normal and diabeticrats. METHOD:Losartan and glimepiride were studied at a dose of 4.5 and 0.09 mg/kg and in normal and diabeticrats, respectively. The blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours and analyzed for glucose levels using a glucometer. RESULTS:Glimepiride exhibited a maximum reduction of blood glucose levels at the 4th hour in normal and diabeticrats. The maximum hypoglycemic effect was observed at the 6th hour in normal rats treated with losartan. In normal rats, losartan did not have any significant effect on the hypoglycemic activity of glimepiride in either the single- or multiple-dose interaction study. In the case of diabeticrats, losartan did not have any significant effect on the hypoglycemic activity of glimepiride in the single-dose interaction study, but a significant change was observed in the multiple-dose study of diabeticrats. Hence, the interaction was found to be pharmacodynamic. CONCLUSIONS: The study indicates that chronic losartan pretreatment elevates the hypoglycemic effect of glimepiride by a possible rise in insulin sensitivity and improving insulin homeostasis or may be due to the inhibition of CYP2C9. The study also suggests that caution may be recommended concerning combined use of losartan and an oral hypoglycemic agent, glimepiride.
Entities:
Keywords:
drug interactions; glimepiride; hypoglycemia; losartan
Authors: E Deininger; K M Oltmanns; P Wellhoener; B Fruehwald-Schultes; W Kern; B Heuer; P Dominiak; J Born; H L Fehm; A Peters Journal: Clin Pharmacol Ther Date: 2001-10 Impact factor: 6.875