Pharmacodynamic and pharmacokinetic interactions of piperine on gliclazide in animal models

Abstract

Back Ground: The objective of the present study was to find out the pharmacodynamic and pharmacokinetic interactions of piperine on gliclazide in rats and rabbits. Methods: Influence of piperine on the activity of gliclazide was determined by conducting single- and multiple-dose interaction studies in rats (normal and diabetic) and diabetic rabbits. Blood samples collected at predetermined time intervals from experimental animals were used for the estimation of glucose and insulin levels by using automated clinical chemistry analyzer and radioimmunoassay method, respectively. β-cell function was determined by homeostasis model assessment. Additionally, serum gliclazide levels in rabbits were analyzed by high-performance liquid chromatography. Results: Gliclazide showed significant reduction in blood glucose levels in diabetic rats and rabbits. Similarly, piperine also showed significant reduction in blood glucose levels in animals. Additionally,, samples analyzed from all time points in combination with piperine showed peak reduction in blood glucose in diabetic rats and rabbits. The pharmacokinetics of gliclazide was also altered by single- or multiple-dose piperine treatments in rabbits. Conclusion: The interaction of piperine with gliclazide upon single and multiple-dose treatment was pharmacodynamic and pharmacokinetic in nature, indicating the need for periodic monitoring of glucose levels and dose adjustment as necessary when this combination is prescribed to diabetic patients.