Pharmacokinetic Drug Food Interaction Study of Nateglinide and Pomegranate Fruit Juice

Objective: Pomegranate juice is inhibitor of CYP450 enzyme system such as CYP2C9 and CYP3A4. The objective of the present study was to determine the consequence of pomegranate fruit juice on the pharmacokinetics of oral hypoglycemic drug nateglinide in rats. Materials and Methods: This is a laboratory study to investigate drug-food interaction effects of Punica granatum fruit juice (3 ml) and nateglinide (in doses 10 and 20 mg/kg body weight, p.o.) in live animals where the effects of food drug interaction on pharmacokinetics parameters such as Cmax and AUC in vehicle and nateglinide and pomegranate juice and nateglinide treated rats was undertaken. Four groups of Wistar albino rats comprising of (n=5) animals in each group were taken and treated with vehicle and nateglinide (in doses 10 and 20 mg/kg body weight, p.o.) pomegranate juice (3ml, p.o.) and nateglinide (in doses 10 and 20 mg/kg body weight, p.o.). Results: The rats which were administered with pomegranate juice + nateglinide (in doses 10 and 20 mg/kg body weight, p.o.) showed  raised Cmax to 2.85 fold and 2.21-fold respectively and an increase in AUC was found to be 1.34 fold and 1.47 fold respectively, when vehicle + nateglinide 10mg/kg and vehicle + 20mg/kg drug treated groups were compared. The results were compared at P-value< 0.01. Conclusion: A significant drug interaction was observed when nateglinide and pomegranate juice was administered indicating caution must be exercised when such food and drug is co-administered as the chance of more hypoglycemia may occur due to this potential drug-food interaction.