Influence of esomeprazole on hypoglycemic activity of oral antidiabetic agents in rats and rabbits

Gastrointestinal symptoms are fairly common in diabetes mellitus. Glimepride, is a latest second generation sulfonylurea used for the treatment of type II diabetes mellitus, is a insulin secrectagogue; indirectly, it also increases insulin secretion and its specific effect on pancreatic ATP-dependent K(+) channel inhibition. Esomeprazole, the (S)-isomer of omeprazole, is the first proton pump inhibitors developed as a single isomer for the treatment of acid-peptic diseases by specific inhibition of H(+)/K(+)-ATPase in gastric parietal cell. Since there is possibility for drug interaction leading to decreased activity of glimepride, the present study was conducted to evaluate the effect of the combination. Studies in normal and alloxan induced diabetic rats were conducted with oral doses of 135 mu g/kg bd.wt. of glimepride, 3.6 mg/kg bd.wt. of esomeprazole, and their combination with adequate washout periods in between treatments. Studies in normal rabbits were conducted with doses 70 mu g/1.5 kg bd. wt. of glimepride, 1.8 mg/1.5 kg bd. wt. of esomeprazole, and their combination given orally. The blood samples were collected at 0, 1, 2, 4, 8, 12, 18, 24 h and analyzed for glucose levels by GOD/POD method and insulin in diabetic rats by radioimmunoassay methods. Glimepride produced hypoglycaemic/antidiabetic activity in normal and diabetic rats activity with peak activity maximum at 4 h and hypoglycemic activity in normal rabbits maximum at 4 h and esomeprazole increases the insulin levels in diabetic rats. The study also suggests the necessity to readjust the dose of glimepride, when used concomitantly with esomeprazole.