Effect of Simvastatin on the Pharmacodynamic Activity of Repaglinide in Rats/Rabbits

Dyslipidemia is common in patients with type 2 diabetes. Statins are used as the first choice in treatment of diabetic dyslipidemia. Simvastatin, an HMG-CoA reductase inhibitor, is widely used in the treatment of hypercholesterolemia. Repaglinide is a short-acting, oral, insulin secretagogue that is used in the treatment of type 2 diabetes mellitus. Both the category of drugs undergo extensive metabolism with cytochrome P450 enzyme system. This may lead to drug-drug interaction problems with altered repaglinide activity which is unwanted. Simvastatin/repaglinide/simvastatin+repaglinide were administered orally to normal, diabetic rats, and to normal rabbits. Blood samples were collected at different time intervals and were analyzed for blood glucose by GOD–POD method using commercial glucose kits and repaglinide estimation in plasma by HPLC method. Diabetes was induced by alloxan 100 mg/kg body weight administered by I.P route. Simvastatin + repaglinide produced hypoglycemic activity in a dose dependant manner in normal and diabetic condition. In the presence of simvastatin, repaglinide blood glucose lowering activity was not increased significantly (P<0.05) compared with repaglinide matching control. The present study concludes co-administration of simvastatin was not improved repaglinide responses significantly in animal models.