Effect of Umbelliferone on pharmacokinetic and pharmacodynamic parameters of Glibenclamide in Streptozocin induced diabetic rats

The present investigation aims to determine the effect of Umbelliferone (UMB) on pharmacokinetic (PK) and pharmacodynamic (PD) parameters of Glibenclamide (GLB) in diabetic rats. Simultaneously, the effect was studied in normal rats. Diabetes in rats was induced by Streptazocin (STZ). The PK parameters are calculated in normal and diabetic rats. PD studies were performed only on diabetic rats. From the PK results, about 2.0-fold improvement in the oral bioavailability of GLB in diabetic rats was observed when treated with GLB in normal rats. A single-dose (SD) and multi-dose (MD) administration of GLB + UMB showed about 3.8 and 4.0-fold enhancement in oral bioavailability of GLB, respectively in the diabetic group compared with the normal GLB-treated group. Similarly, SD and MD of GLB + UMB showed 2.8-folds and 2.7-folds, respectively in diabetic rats when compared with SD and MD of GLB + UMB in normal rats. Further, the rate of clearance and also the volume of distribution significantly changed in diabetic rats. No significant differences were observed in the PK parameters of SD and MD of GLB+ UMB treated groups in diabetic rats. The blood glucose levels were significantly (p<0.05) reduced (12.0 and 13.5% after SD and MD of GLB + UMB treatment, respectively) compared to GLB alone treated diabetic rats during a period of 24 h were noticed from PD studies. The maximum reduction was observed at 2 h (44.3 and 45.6 % after SD and MD of GLB + UMB treatment, respectively) compared with standard GLB treatment (32.1%).