Pharmacokinetic Interaction of Gliclazide with Ornidazole in Healthy Albino Wistar Rats

Abstract

Background: Gliclazide is a widely used drug for the treatment of type 2 diabetes. Retrospective studies shows that diabetics are at increased risk of suffering severe complications after amoebic infection. Ornidazole is a widely used antiamoebic drug. The objective of this study was to examine the effect of oral administration of ornidazole on blood glucose levels, investigate its effect on the activity and pharmacokinetics of gliclazide in normal rats and to evaluate the safety and effectiveness of the combination. Methods: Studies in normal rats were conducted with oral doses of 2 mg/kg body weight of gliclazide and 25 mg/kg body weight of ornidazole andin combination. Blood samples were collected at regular time intervals from rat’s orbital sinuses. All the blood samples were analysed for blood glucose by glucose oxidase/peroxidase (GOD/POD) method and HPLC was used to understand the pharmacokinetics of gliclazide alone and in combination with ornidazole. Results: The results of the present study is indicating that ornidazole does not possess glucose lowering activity therefore it may be inferred that drug-drug interaction of ornidazole with gliclazide is pharmacokinetic type and the possible interaction may be due to CYP2C9 inhibition. Gliclazide produced glucose lowering activity in normal rats with peak activity at 2 h. In combination, ornidazole increases the effect of gliclazide in rats. Conclusion: Thus, it can be concluded that the combination of ornidazole and gliclazide may need slight dose adjustment and care should be taken when the combination is prescribed for their clinical benefit in diabetic patients. However, further studies are warranted. Key words: Albino wistar rats, Cytochrome P 2C9, Gliclazide, HPLC (High Performance Liquid Chromatography), Pharmacokinetic interactions.