Effect of atorvastatin on pharmacology of sitagliptin in streptozotocin-nicotinamide induced type-II diabetes in rats

Abstract

Prolonged type 2 diabetes mellitus (Type2DM) may lead to high risk of cardiovascular disease (CVD) requiring a global therapeutic approach. Statin therapy has proven its efficacy in reducing CVD events in Type2 DM patients. Dipeptidyl peptidase-4 inhibitors (gliptins), which are increasingly used to target hyperglycemia. In the present study type 2 DM in rats by i.p. Administration of Streptozotocin (STZ); (60 mg/kg) -Nicotinamide (120 mg/kg). Diabetes induced rats were divided into groups and treated with Sitagliptin alone and in combination with atorvastatin for 7 days. Blood samples were collected by retro orbital puncture. Mean glucose concentration was measured by GOD-POD method using commercial glucose kits and sitagliptin in plasma was estimated by RP-HPLC method using methanol: water (60:40 v/v, containing 10 mM Tris and 10 mM Triethylamine) was adjusted to pH 9.0 using 1 mol/L hydrochloric acid. The blood glucose lowering activity of sitagliptin was increased by the presence of atorvastatin in diabetic rats. The pharmacokinetic (PK) and pharmacodynamic (PD) parameters of sitagliptin in diabetic rats were significantly changed in the presence of atorvastatin. The present study concludes that co-administration of atorvastatin with sitagliptin significantly improved the responses of sitagliptin in diabetic rats. Improved glucose metabolism and increased sitagliptin levels due to competitive inhibition of CYP 3A4 enzyme by atorvastatin may be responsible for the improved anti-hyperglycemic activity of sitagliptin.