Drug-Drug Interaction between Pravastatin and Gliclazide in Animal Models

Abstract

The present study is planned to evaluate the safety of gliclazide (antidiabetic) therapy in the presence of pravastatin (antihyperlipidemic) in rats and rabbits. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide, pravastatin, and their combination. Similarly, studies in normal rabbits were conducted with oral doses of gliclazide, pravastatin, and their combination with adequate washout periods in between the treatments. Blood samples were collected from rats and rabbits at different time intervals and were analyzed for blood serum gliclazide levels. Gliclazide produced hypoglycaemic/antihyperglycaemic activity in normal and diabetic rats with peak activity after 2 hours and 8 hours and hypoglycaemic activity in normal rabbits with peak activity after 3 hours. Pravastatin alone produced minor reduction in blood glucose levels in normal rats/diabetic rats/normal rabbits. Pravastatin increased the hypoglycaemic effect of gliclazide in normal rats/diabetic rats/normal rabbits when administered together. The serum insulin levels were increased with pravastatin treatment in rabbits. The serum gliclazide levels and pharmacokinetic parameters of gliclazide were altered significantly in presence of pravastatin in rabbits. The interaction observed appears to be pharmacokinetic interaction at metabolic and excretion levels.