Interaction Studies between Sitagliptin Phosphate and Atorvastatin Calcium in Streptozotocin Induced Chronic Type II Diabetes Mellitus Rat Model

Abstract

Diabetes Mellitus describes a metabolic disorder which is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion. Various combination therapies are used to treat metabolic syndrome and includes an antidiabetic drug to control the blood glucose levels, anti-hyperlipidemic drug to control cholesterol and lipid levels. In this study interaction between Sitagliptin phosphate, drug from antidiabetic class i.e. dipeptidyl peptidase IV inhibitor and Atorvastatin calcium other from antihyperlipidemic class i.e. HMG-COA reductase inhibitor was evaluated in Streptozotocin and High-fat diet induced type II diabetic rat model. The combination was selected since Sitagliptin phosphate and Atorvastatin Calcium share a common metabolizing enzyme, CYP3A4, there might be chances of interaction taking place due to the co-administration of the same. Bioanalytical method was developed and validated according to ICH guidelines for evaluation of pharmacokinetic parameters. Pharmacodynamic parameters such as Serum glucose, Serum cholesterol, Serum triglyceride levels and other related tests were performed to evaluate interaction at pharmacodynamic level. Results suggest that, at pharmacodynamic and pharmacokinetic level, this combination treatment can have good application in managing blood glucose level and lipid level as well. Being not affected by the CYP450 metabolisms as when correlated with plasma levels at their particular half-life, we suggest that Sitagliptin phosphate and atorvastatin calcium on simultaneous administration will not lead to cause any toxic effect..