Molecular and Cellular Biochemistry

, Volume 354, Issue 1–2, pp 135–140 | Cite as

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

  • Prashant D. Phadatare
  • V. M. Chandrashekhar


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.


Esomeprazole 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. 1.
    Ramesh KG, Parloop AB, Mahesh DB (2004) Elements of clinical pharmacy, 1st edn. BS Shah Prakashan, Ahmedabad, pp 135–148Google Scholar
  2. 2.
    Kubacka KJ, Antal AL, Juhl RP (1987) Paradoxical effect of cimetidine and ranitidine on glibenclamide pharmacokinetic and pharmacodnamics. Br J Clin Pharmacol 23:743–751PubMedGoogle Scholar
  3. 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
  4. 4.
    Prichard PJ, Wait RP, Kitchingman GK, Somerville KW, Langman MJ, Williams J et al (1987) Oral phenytoin pharmacokinetics during omeprazole therapy. Br J Clin Pharmacol 24:543–545PubMedGoogle Scholar
  5. 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
  6. 6.
    Hassan-Alin M, Adersoon T, Bredberg E, Rohss K (2000) Pharmacokinetics of esomeprazole after oral and intravenous administration of single and repeated doses to healthy subjects. Eur J Clin Pharmacol 56:665–670CrossRefPubMedGoogle Scholar
  7. 7.
    Drager E (1995) Clinical profile of glimepride. Diabet Res Clin Pract 28(Suppl:S):138–139Google Scholar
  8. 8.
    Song DK, Ashcroft FM (2001) Glimepride block cloned β-cell, cardic and smooth muscle K+ATP channels. Br J Pharmacol 133(1):193–199CrossRefPubMedGoogle Scholar
  9. 9.
    Klepzig H, Kobert G, Matter C, Luss H, Schneider H et al (1999) Sulfonylureas and ischemic preconditioning, A double-blind, placebo-controlled evaluation of glimepride and glibenclamide. Eur Heart J 20(6):439–446CrossRefPubMedGoogle Scholar
  10. 10.
    Sane RT, Mnon SN, Shafi Inamdar et al (2004) Simultaneous determination of pioglitazone and glimepride by high-performance liquid chromatography. Chromatographia 59:451–453CrossRefGoogle Scholar
  11. 11.
    Esplugues JV, Marthi-Cabrera M, Ponce J (2006) Safety of proton pump inhibitors. Med Clin (Barc) 127:790–795CrossRefGoogle Scholar
  12. 12.
    Larsson H, Carlsson E, Junggren U, Olbe L, Sjostrand SE, Skanberg I, Sundell G (1983) Inhibition of gastric acid secretion by omeprazole in dog and rat. Gastroenterology 85(4):900–907PubMedGoogle Scholar
  13. 13.
    Satoh H, Inatomi N, Nagaya H, Inada I, Nohara A, Nakamura H (1989) Antisecretory and antiulcer activites of a novel proton pump inhibitors AG-1749 in dogs and rats. J Pharmacol Exp Ther 248:806–815PubMedGoogle Scholar
  14. 14.
    Bastaki SalimMA, Chandranath IrwinS, Singh Jaipaul (2008) The anti-secretory and anti-ulcer activities of esomeprazole in comparison with omeprazole in the stomach of rats and rabbits. Mol Cell Biochem 309:167–175CrossRefPubMedGoogle Scholar
  15. 15.
    Lawrence DR, Bacharach AL (1964) Evaluation of drug activities. In: Pharmacometrics, vol I. Academic Press, New York, USAGoogle Scholar
  16. 16.
    Riley V (1960) Adaption of orbital bleeding technique to rapid serial blood studies. Proc Soc Exp Bio Med 104:751–754Google Scholar
  17. 17.
    Trinder P (1969) Determination of blood glucose using an oxidase-peroxidase system with a non carcinogenic chemogen. J Clin Pathol 22:158–161CrossRefPubMedGoogle Scholar
  18. 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
  19. 19.
    Venkatesh S, Reddy DG, Reddy BM, Ramesh M, Rao AV (2003) Antihyperglycemic activity of Caralluma attenuate. Fitoterpia 74:274–279CrossRefGoogle Scholar
  20. 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
  21. 21.
    Giuseppe D, Arrigo FG, Cicerob AntonioG, Pietro RD et al (2005) A comparison of the effect of pioglitazone and rosiglitazone combined with glimepride on prothrombotic state in type 2 diabetic patients with the metabolic syndrome. Diabetes Res Clin Pract 69(1):5–13CrossRefGoogle Scholar
  22. 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
  23. 23.
    Satyanarayana S, Kilari EK (2006) Influence of nicorandil on the pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits. Mol Cell Biochem 291:101–105CrossRefPubMedGoogle Scholar
  24. 24.
    Gribble FM, Reimann F (2003) Differential selectivity of insulin secrectagogues: mechanisms, clinical implications, and drug interactions. J Diabetes Complicat 17(2):11–15CrossRefPubMedGoogle Scholar
  25. 25.
    Rajan AS, Aguilar-Bryan L, Nelson DA, Yaney GC, Hsu WH, Kunze DL, Boyd AE (1990) Ion channels and insulin secretion. Diabetes Care 13(3):340–363CrossRefPubMedGoogle Scholar
  26. 26.
    Klotz U (2000) Pharmacokinetic considerations in the eradication of Helicobacter pylori. Clin Pharmacokinet 38(3):243–270CrossRefPubMedGoogle Scholar
  27. 27.
    Campbell RK (1998) Glimepride: role of a new sulfonylurea in the treatment of type 2 diabetes mellitus. Ann Pharmcother 32(10):1044–1052CrossRefGoogle Scholar
  28. 28.
    Gunter M, Detlev H, Jurgen P, Raymond O, Werner K (1994) Differential interaction of glimepride and glibenclamide with the β-cell sulphonylurease receptor I. Binding characteristics. Biochem et Biophysica Acta 1191:267–277CrossRefGoogle Scholar
  29. 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

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© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  1. 1.Post Graduate Department of Pharmacology and Research CentreH. S. K. College of PharmacyBagalkotIndia

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