title: Influence of esomeprazole on hypoglycemic activity of oral antidiabetic agents in rats and rabbits.
abstract: 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 μg/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 μg/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.
authors.affiliation: Post Graduate Department of Pharmacology and Research Centre, H. S. K. College of Pharmacy, Bagalkot, Karnataka 587101, India. prashantphadatare@gmail.com
authors.forename: Prashant D
authors.initials: PD
authors.lastname: Phadatare
authors.forename: V M
authors.initials: VM
authors.lastname: Chandrashekhar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D057075:Enzyme Assays; D064098:Esomeprazole; D005260:Female; D005949:Glucose Oxidase / Q000097:blood; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D009853:Omeprazole / Q000494:pharmacology / Q000627:therapeutic use*; D009195:Peroxidase / Q000097:blood; D011817:Rabbits; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; C057619:glimepiride; D005949:Glucose Oxidase; D009195:Peroxidase; D009853:Omeprazole; D064098:Esomeprazole