Skip to main content
SpringerLink
Log in

Influence of nicorandil on the pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Chronic diabetes precipitates ischaemic heart disease (IHD) and many other disorders. IHD inturn is shown in the form of angina initially. According to EUROPA study, the incidence of angina is high in type II diabetics. Gliclazide, a second generation sulphonylurea derivative is widely used in the treatment of type-II diabetes and is known to release insulin by K+ channel inhibition. Nicorandil, a newer antianginal drug widely used now a days acts by opening potassium channels in the cardiac muscle cell and also by releasing nitric oxide. However its action on pancreatic cell K+ channel is not known. Since there is possibility for drug interaction leading to decreased activity of gliclazide 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 2 mg/kg bd. wt. of gliclazide, 1.8 mg/kg bd. wt. of nicorandil and their combination with adequate washout periods in between treatments. Studies in normal rabbits were conducted with 5.6 mg/1.5 kg bd. wt. of gliclazide, 1.4 mg/1.5 kg bd. wt. of nicorandil and their combination given orally. Blood samples were collected in rats from retro orbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h and by marginal ear vein puncture in rabbits at 0, 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 h. All the blood samples were analysed for glucose by GOD/POD method. The blood samples of rabbits were analysed by HPLC for gliclazide.

Gliclazide produced hypoglycaemic/antidiabetic activity in normal and diabetic rats with peak activity at 1 h and 8 h and hypoglycaemic activity in normal rabbits at 3 h, while nicorandil alone produced significant hyperglycaemia at 4 h and reduced the effect of gliclazide with no significant change in pharmacokinetics when administered in combination. The interaction observed appears to be pharmacodynamic at the receptor level as expected.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Morrish NJ, Wang SI, Stevens LK, Fuller JH, Keen H: WHO Multinational Study Group: Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetalogia 44: S14–S21, 2001

    Article  Google Scholar 

  2. Mohan V, Premalatha G, Sastry NG: Ischaemic heart disease in south Indian NIDDM patients-A clinic based study on 6597 NIDDM patients. Int J Diab Dev Countries 15: 64–67, 1995

    Google Scholar 

  3. Goodman LS, Gilman A: The pharmacological basis of therapeutics, 10th ed. (McGraw-Hill, New York, 2001)

    Google Scholar 

  4. Fox KM, Henderson JR, Bertrand ME, et al.: The European trial on reduction of cardiac events with perindoril in stable coronary artery disease (EUROPA). Eur Heart J 19: J52–J55, 1998

    Article  PubMed  CAS  Google Scholar 

  5. Schernthaner G: Gliclazide modified release: A critical review of pharmacodynamic, metabolic and vasoprotective effects. Metabolism 52: 29–34, 2003

    Article  PubMed  CAS  Google Scholar 

  6. Song DK, Ashcroft FM: Glimepiride block of cloned β cell, cardiac and smooth muscle K+ ATP channels. Br J Pharmacol 133: 193–199, 2001

    Article  PubMed  CAS  Google Scholar 

  7. Gribble FM, Tucker SJ, Seino S, Ashcroft FM: Tissue specificity of sulfonylureas: Studies on cloned cardiac and beta-cell K(ATP) channels. Diabetes 47: 1412–1418, 1998

    PubMed  CAS  Google Scholar 

  8. Jennings PE, Belch JJF: Free radical scavenging activity of sulphonylureas: a clinical assessment of the effectiveness of gliclazide. Ter Arkh 73: 27–31, 2001

    PubMed  CAS  Google Scholar 

  9. Brien RC, Luo M, Balazs N, Mercuri J: In vitro and in vivo antioxidant properties of gliclazide. J Diabetes Complications 14: 201–206, 2000

    Article  PubMed  Google Scholar 

  10. Homes B, Heel RC, Brogden RN, Speight TM, Avery GS: Gliclazide – A preliminary review of its pharmacodynamic properties and therapeutic efficacy in diabetes mellitus. Drugs 27: 301–327, 1984

    PubMed  Google Scholar 

  11. Harrower AD: Comparative tolerability of sulphonylureas in diabetes mellitus. Drug Saf 22: 313–320, 2000

    Article  PubMed  CAS  Google Scholar 

  12. Harrower AD: Efficacy of gliclazide in comparision with other sulphonylureas in the treatment of NIDDM. Diabetes Res Clin Pract 14: S65–S67, 1991

    Article  PubMed  Google Scholar 

  13. Ziegler O, Drouin P: Hemobiological properties of gliclazide. J diabetes complications 8: 235–239, 1994

    Article  PubMed  CAS  Google Scholar 

  14. Palmer KJ, Brogden RN: Gliclazide: an update of its pharmacological properties and therapeutic efficacy in non-insulin-dependent diabetes mellitus. Drugs 46: 92–125, 1993

    PubMed  CAS  Google Scholar 

  15. Fava D, Cassone-Faldetta M, Laurenti O, De luca O, Ghiselli A, De Mattia G: Gliclazide improves antioxidant status and nitric oxide mediated vasodilation in type-2 diabetes. Diabet Med 19: 752–757, 2002

    Article  PubMed  CAS  Google Scholar 

  16. Kishida H, Murao S: Effect of a new coronary vasodilator, nicorandil on variant angina pectoris. Clin Pharmacol Ther 42: 166–174, 1987

    Article  PubMed  CAS  Google Scholar 

  17. Effect of nicorandil on coronary events in patients with stable angina: The Impact of Nicorandil in Angina (IONA) randamised trial. Lancet 359: 1269–1275, 2002

  18. Tao Jun, Catalano M: Nitric oxide is involved in the insulin release in rats by l-arginine. International Journal of Angiology 6: 0187–0189, 1997

    Google Scholar 

  19. Denis Roy, Mylene Perreault, Andre Marette: Insulin stimulation of glucose uptake in skeletal muscles and adipose tissue in vivo is nitric oxide dependent. Am J Physiolol 274: E692–E699, 1998

    CAS  Google Scholar 

  20. Riley V: Adaptation of orbital bleeding technique to rapid serial blood studies. Proc Soc Exp Biol Med 104: 751–754, 1960

    PubMed  CAS  Google Scholar 

  21. Trinder P: Determination of blood glucose using an oxidase-peroxidase system with a non carcinogenic chemogen. J Clin Pathol 22: 158–161, 1969

    PubMed  CAS  Google Scholar 

  22. Heikkila RE: The prevention of alloxan-induced diabetes in mice by dimethyl sulfoxide. Eur J Pharmacol 44: 191–193, 1977

    Article  PubMed  CAS  Google Scholar 

  23. Gribble FM, Reimann F: Differential selectivity of insulin secretogogues: Mechanism, clinical implications and drug interactions. J Diabetes complications 17: 11–5, 2003

    Article  PubMed  Google Scholar 

  24. Rajan AS, Aguilar-Bryan L, Nelson DA, Yaney GC, Hsu WH, Kunze DL, Boyd AE: Ion channels and insulin secretion. Diabetes Care Mar 13: 340–363, 1990

    CAS  Google Scholar 

  25. Miyazaki H, Fijii T, Yoshida K, Arakawa S, Furukawa H: Disposition and metabolism of [3H] gliclazide in rats. Eur J Drug Metab Pharmacokinet 8: 117–131, 1983

    Article  CAS  Google Scholar 

  26. Viggneri R., Pezzino V., Wang KY: Comparison of the in-vitro effect of biguanides and sulfonylureas on the insulin binding of its receptors in target cells. J Clin Endocrinol Metab 54: 95–100. 1982

    Article  PubMed  Google Scholar 

  27. Campbell DB, Lavielle R, Nathan C: The mode of action on clinical pharmacology of gliclazide a review. Diabetes Res Clin Pract 14: S21–S36, 1991

    Article  PubMed  Google Scholar 

  28. Chiasson JL, Hamet P, Vercly M: The effect of Diamicron (R) on the secretion and action of insulin. Diabetes Res Clin Pract 14: S47–S51, 1991

    Article  PubMed  CAS  Google Scholar 

  29. Ma A, Kamp M, Bird D: The effects of long term gliclazide administration on insulin secretion and insulin sensitivity. Aus NZ J Med 19: 44–49, 1989

    CAS  Google Scholar 

  30. Vanhaeften TW, Vaneman TF, Gerich JE: Influence of gliclazide on glucose stimulated insulin release in man. Metabolism 40: 751–755, 1991

    Article  PubMed  CAS  Google Scholar 

  31. Wajchenberg BL, Santomano ATMG, Porrelli RN: Effect of sulfonylurea (gliclazide) treatment on insulin sensitivity and glucose mediated, glucose disposal in patients with non-insulin dependent diabetes mellitus (NIDDM). Diabetes Res Clin Pract 20: 147–154, 1993

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmacology Division, Department of Pharmaceutical Sciences, Andhra University, Visakhapatnam, 530 003, Andhra Pradesh, India

    S. Satyanarayana & Eswar K. Kilari

Authors
  1. S. Satyanarayana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eswar K. Kilari
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Satyanarayana, S., Kilari, E.K. Influence of nicorandil on the pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits. Mol Cell Biochem 291, 101–105 (2006). https://doi.org/10.1007/s11010-006-9202-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-006-9202-y

Keywords

Search

Navigation