INFLUENCE OF NEVIRAPINE ON THE PHARMACODYNAMICS AND PHARMACOKINETICS OF REPAGLINIDE IN RATS AND RABBITS

Abstract

Introduction: Management of HIV/AIDS is gradually expanding to include the chronic and metabolic complications and the adverse effects associated with its treatments like Type II diabetes mellitus. Repaglinide is a novel oral hypoglycemic agent chemically unrelated to sulphonylureas, metformin or acarbose used for the treatment of type II diabetes. Nevirapine is widely used non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection. Objective: The objective of this study was to examine the effect of oral administration of nevirapine on blood glucose and investigate their effect on the activity of repaglinide and to evaluate the safety and effectiveness of the combination. Materials and Methods: Studies in normal, diabetic rats and normal rabbits were conducted with oral doses of repaglinide, nevirapine and their combination. All the animals were fasted for 18 h prior to experimentation; during this period the animals were fed with water ad libitum. The blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours in rats by retro orbital puncture and by marginal ear vein puncture in rabbits at different time intervals. Further, the samples were analyzed for glucose by glucose oxidase/peroxidase (GOD/POD) method. The rabbit blood samples were analyzed by HPLC for serum repaglinide concentration. The serum repaglinide levels and pharmacokinetic parameters of repaglinide were evaluated with multiple dose treatments of nevirapine in rabbits. Result and Discussion: Nevirapine alone have no significant effect on the blood glucose level in rats and rabbits. Repaglinide produced hypoglycemic and antihyperglycemic activity in normal and diabetic rats with peak activity at 2 h and hypoglycemic activity in normal rabbits at 1.5 h. In combination, nevirapine reduced the effect of repaglinide in rats and rabbits. The interaction was found to be significant at both pharmacodynamic as well as at pharmacokinetic levels. Conclusion: Thus, it can be concluded that the combination of nevirapine and repaglinide may need dose adjustment and care should be taken when the combination is prescribed for their clinical benefit in diabetic patients. However, further studies are warranted.