Abstract

The present work studied the influence of esomeprazole (Eso) on the pharmacokinetics (PK) and Pharmacodynamic (PD) of glipizide (Gli) in nondiabetic and diabetic animal models to evaluate the safety and effectiveness of the combination. Studies were conducted in normal and alloxan induced diabetic guinea pigs. Diabetes was induced by a single intraperitoneal injection of alloxan (200 mg/kg), and then glipizide and esomeprazole were administered orally for 7 days. On 8th day, the blood samples were collected at regular time intervals and the pharmacodynamic and pharmacokinetic parameters of glipizide, before and after esomeprazole treatment were determined. The blood glucose levels were estimated by Glucose Oxidase-Peroxidase (GOD-POD) method. Esomeprazole treatment has shown maximum antidiabetic effect at 6th hour after oral administration. Pretreatment with esomeprazole for seven days resulted in significant hypoglycemic effect of glipizide when compared with glipizide alone in both diabetic and normal animals. Esomeprazole has shown significant increase in pharmacokinetic profile of glipizide in both single and multiple days treatment. Present study results suggested that, esomeprazole significantly increases the concentration and AUC (area under curve) of glipizide due to inhibition of Cytochrome P-450 (CYP) enzyme. Hence, the present study indicated that esomeprazole has potential effect on pharmacokinetics and pharmacodynamics of glipizide.