Drug–drug interaction between esomeprazole at therapeutic and higher doses and sulfonylureas was studied. Sulfonylureas (tolbutamide 40 mg/kg and glibenclamide 40 µg/kg) were administered and the time to onset of hypoglycemia, the duration of the hypoglycemia, and the peak hypoglycemia were determined. Esomeprazole (1.8 mg/kg, 3.6 mg/kg, and 30 mg/kg) was administered for 8 days and its influence on sulfonylurea-induced hypoglycemia was studied. Therapeutic doses of esomeprazole, i.e., 1.8 mg/kg and 3.6 mg/kg dose did not influence the hypoglycemia induced by sulfonylureas. However, a higher dose, i.e., 30 mg/kg, did significantly enhance the duration of hypoglycemia and the peak hypolgycemia. Esomeprazole (30 mg/kg) by itself did not reduce the blood glucose levels; therefore, a pharmacodynamic type of drug interaction can be ruled out. Similarly, a pharmacokinetic type of drug interaction may be ruled out at therapeutic doses. The CYP isoenzyme system involved in the metabolism of sulfonylureas are not very sensitive to esomeprazole and the dose and frequency of administration of sulfonylurea need not be readjusted when they are used concomitantly with esomeprazole (at therapeutic doses)
