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 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.
KeywordsEsomeprazole Glimepride Drug interaction
The authors are thankful to Aurochem Pharmaceutical, Palghar and Alcon Bioscence, Vapi for supplying gift samples of glimepride and esomeprazole, respectively.
- 1.Ramesh KG, Parloop AB, Mahesh DB (2004) Elements of clinical pharmacy, 1st edn. BS Shah Prakashan, Ahmedabad, pp 135–148Google Scholar
- 3.Rajendra SV, Raghaveergupta PS, Joshi VG, Anand Kumar Y, Venkantrao N, Ramchandra Setty S (2004) Influence of lansoprazole on hypoglycemic activity of oral antidiabetic agent in healthy albino rats. Acta Pharm Turc 46:95–99Google Scholar
- 5.Kumar V, Venakat Rao N, Ramachandra Setty S (2000) Influence of omeprazole on hypoglycemic activity of glibenclamide and tolbutamide normal albino rabbits. Acta Pharm Turc 42:135–138Google Scholar
- 7.Drager E (1995) Clinical profile of glimepride. Diabet Res Clin Pract 28(Suppl:S):138–139Google Scholar
- 15.Lawrence DR, Bacharach AL (1964) Evaluation of drug activities. In: Pharmacometrics, vol I. Academic Press, New York, USAGoogle Scholar
- 16.Riley V (1960) Adaption of orbital bleeding technique to rapid serial blood studies. Proc Soc Exp Bio Med 104:751–754Google Scholar
- 18.Manonmani G, Bhavapriya V, Kalpana S, Govindasamy S, Apparanantham T (2005) Antioxidant activity of Cassia fistula (Linn.) flowers in alloxan induced diabetic rats. J Ethno Pharmacol 97(1):39–42Google Scholar
- 20.Satyanarayana S, Nitin M, Prasad K (2007) Pharmacodynamic and pharmacokinetic drug interaction of disopyramide with tolubutamide in rabbits. Indian drugs 44(9):683–688Google Scholar
- 22.Olbrich HG, Muller M, Lindner S, Henke B, Zarse M, Riehle M, Oremek G, Mutschler E (1999) Glimepride inhibits the rilmakalim induced decrease in intracellular free calcium and contraction of isolated heart muscle cells from guinea pigs to a lesser extent than glibenclamide. Int J Cardiol 72:53–63CrossRefPubMedGoogle Scholar
- 29.Langtry HD, Balfour JA (1998) Glimepride, a review of its use in the management of type 2 diabetes mellitus. Drugs 55:563–584Google Scholar