In vivo Studies On Drug _Drug Interactions Of Antagonistic Valsartan On Gliclazide And Metformin In Normal And Streptozotocin Induced Diabetic Rats

Abstract

Metformin and Gliclazide are now being recognized as the standard therapy in type 2 Diabetes patients. These drugs has many drug-drug interactions that can increase the risk of patient s conditions. Therefore this study was conducted to evaluate any possible pharmacokinetic interactions between these antidiabetic drugs and the Valsartan drug used for the treatment of hypertension. The rats were fasted overnight before inducing diabetes with streptozotocin. The rats were given an intraperitoneal injection of streptozotocin (50 mg kgand#8722;1) freshly prepared in 0.1M sodium citrate buffer. The diabetic state was confirmed 48 h after streptozotocin injection. Diabetic rats were grouped into four groups each group of six rats and one normal control group (diabetic control group). RP-HPLC method was developed for the simultaneous estimation of Metformin-Valsartan and Gliclazide-Valsartan to estimate possible pharmacokinetic parameters of these drugs after oral administration. There were no significant difference in the tmax of only Metformin, only Gliclazide and combination with Valsartan on day 1 and day 8 respectively. There were no significant increase in both AUC(0 t) and AUC (o-inf) of only Metformin, Metformin along with Valsartan and only Gliclazide, Gliclazide along with Valsartan on day 1 and day 8 respectively. Similarly there were no significant difference observed in the Cmax, tmax and t½ values between individual administration of Metformin and Gliclazide as well as in combination with on day 1 and day 8 respectively. In the present study, based on the results it can be concluded that the concurrent administration of theseantidiabetic drugs along with Valsartan have potential benefit in the treatment of Diabetes and hypertension.