Evaluation of drug-drug interaction on concomitant administration of anti-diabetics and hypolipidemics in in vivo models

摘要

Diabetes mellitus is a multifactorial pathological condition, often associated with co-morbid condition of hyperlipidemia. Anti-diabetics and hypolipidemics are thus co-prescribed. Now, this use of multiple drugs or polypharmacy, however, increases the propensity of drug-drug interactions and adverse drug reactions. Present study was aimed to evaluate the effect of concomitant therapy of anti-diabetics and hypolipidemics on animal models induced with comorbid conditions of diabetes and hyperlipidemia. Diabetes was induced by Streptozotocin and Nicotinamide and hyperlipidemia was induced by High Fat Diet. Comorbid condition of both diabetes and hyperlipidemia was developed in rats. The rats were treated with antidiabetic drug Metformin and hypolipidemic drug Atorvastatin for 28 days. The safety and efficacy of concomitant therapy was evaluated by different biomarkers in serum and antioxidant levels in hepatic and renal tissues, collected from the rats. It was observed that concomitant therapy of Metformin and Atorvastatin was able to restore the blood glucose and triglyceride level by 69.93% and 54.61%, respectively. Concomitant therapy, however, was accompanied by increased oxidative stress in tissues, characterized by altered antioxidant levels. The hepatic and renal glutathione was diminished by 67.6% and 79.7% respectively, whereas, malondialdehyde level was enhanced by 31.7% and 83.3%, indicating oxidative stress induced tissue damage. This preliminary study was an attempt to mimic the comorbid diseased condition in animal model and to evaluate the safety and efficacy of concomitant therapy in animals that can be translated in human system to optimize therapeutic regimen.