Effect of Capsaicin on Pharmacodynamic and pharmacokinetics of Gliclazide in Animal models with Diabetes

Background: Food–drug interactions can have great effect on the adverse effects of many drugs and also on the success of drug treatment. Gliclazide is one of the drugs of choice to treat type 2 diabetes. Capsaicin is present in Capsicum annuum, a spice found in regular food. Objective: The objective of the present study was to find out the pharmacodynamic (PD) and pharmacokinetic (PK) interactions of capsaicin on gliclazide in animal models using rats and rabbits. Materials and Methods: Single‑ and multiple‑dose interaction studies were conducted in rats (normal and diabetic) and rabbits (diabetic) to evaluate the effect of capsaicin on the activity of gliclazide. Blood samples collected at predetermined time intervals from the experimental animals were used for the estimation of glucose and insulin levels using an automated clinical chemistry analyzer and radioimmunoassay method, respectively. β‑cell function was determined by homeostasis model assessment. In addition, high‑performance liquid chromatography technique was used to analyze the serum gliclazide levels in rabbits. Results: Capsaicin did not exhibit any hypoglycemic activity in normal rats, but exhibited significant antihyperglycemic activity in both diabetic rats and rabbits with improvement in insulin levels and β‑cell function. Gliclazide showed significant reduction in blood glucose levels in normal and diabetic rats and diabetic rabbits. In addition, it significantly increased insulin levels and β‑cell function in diabetic animals. The samples analyzed from all time points in combination with capsaicin showed significantly greater reduction in blood glucose levels and a significant increase in insulin levels and β‑cell function in diabetic rats and rabbits. The PK parameters of gliclazide were also altered by capsaicin treatment in rabbits. Conclusion: The present study concluded that the interaction of capsaicin with gliclazide on single‑ and multiple‑dose treatment was both PD and PK in nature.