Influence of Single and Multi Dose Treatment of Glipizide on Pharmacokinetics and Pharmacodynamics of Irbesartan in Normal and Hypertensive Rats

  • Adepu Anusha
  • Dudhipala Narendar
  • Boini Krishna Murthy
  • Puchchakayala GoverdhanEmail author
Original Article



The present study was carried out to investigate the pharmacokinetic and pharmacodynamic drug interaction of irbesartan with glipizide after single and multi dose treatment in normal and hypertensive rat models to evaluate the safety and effectiveness of the combination.


The study was conducted on normal and 10% fructose solution induced hypertensive rats. Irbesartan and glipizide were administered orally for 7 days and on 8th day blood samples were collected for 12 h at regular time intervals from irbesartan alone and in combination with glipizide treated groups. The blood samples were analyzed for various pharmacokinetic and pharmacodynamic parameters.


Irbesartan caused marked reduction in blood pressure in hypertensive rats. The combination of irbesartan and glipizide in hypertensive rats produce significant change in blood pressure (pharmacodynamic) and also significance in pharmacokinetic parameters of irbesartan with glipizide in single dose and multiple doses.


The results of present study demonstrated that the synergistic activity of irbesartan with glipizide was observed.


Irbesartan Glipizide Pharmacokinetic Pharmacodynamic Antihypertensive activity 



We would like to thank management of Vaagdevi College of Pharmacy, Warangal for providing all facilities. Authors were also thankful to A.I.C.T.E for providing fund for lab under MODROBS scheme (8024/RIFD/MOD-354(PVT)/policy-III/2011-2012).

Compliance with Ethical Standards


This study was not funded.

Conflict of Interest

Authors declares there is no conflict of interest.

Ethical approval

Prior the investigation, all the animal experiments were reviewed and approved by the Institutional Animal Ethical Committee (IEAC), Vaagdevi pharmacy college, Warangal, India (1047/ac/07/CPCSEA, Dated 24-04-2007). All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


  1. 1.
    Asif H, Parminder SB. A review of pharmacological and pharmaceutical profile of irbesartan. Int Res J. 2011;2(6):276–86.Google Scholar
  2. 2.
    Bertilsson L, Du Y. Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquineand S-mephenytoin. Clin Pharmacol Ther. 1992;51:388–97.CrossRefPubMedGoogle Scholar
  3. 3.
    Dai S, McNeill JH. Fructose-induced hypertension in rats is concentration-and duration-dependent. J Pharmacol Toxicol Methods. 1995;33:101–7.CrossRefPubMedGoogle Scholar
  4. 4.
    David AW. Drug metabolism. In: Thomas LL, David AW, editors. Foye’s principles of medicinal chemistry, vol 6. Philadelphia: Lippincott Williams and Wilkins; 2008. p. 253–326.Google Scholar
  5. 5.
    Gopala TE, Krishna Murthy C, Mayuren A. Pharmacokinetics of gliclazide alone and in combination with irbesartan in rabbits. Res J Pharm Tech. 2008;1(4):418–21.Google Scholar
  6. 6.
    Goyal RK, Joshi SS, Shah TS. Effects of chronic treatment with Nitrendipine in streptozotocin-induced diabetic rats. Ind J Pharm Sci. 1996;58(3):100–5.Google Scholar
  7. 7.
    Hansson L, Zanchetti A, Carruthers S, Dahlof B, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomized trial. Lancet. 1998;351:1755–62.CrossRefPubMedGoogle Scholar
  8. 8.
    Hwang IS, Ho H, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats. Hypertension. 1987;10:512–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Ji YP. Effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide. Clin Pharmcol Ther. 2003;74:334–40.CrossRefGoogle Scholar
  10. 10.
    Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.CrossRefPubMedGoogle Scholar
  11. 11.
    Mangold B, Gielsdorf W, Marino MR. Irbesaran does not affect the steady-state pharmacodynamics and pharmacokinetics of warfarin. Eur J Clin Pharmacol. 1999;55:593–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Rang HP, Dale MM, Ritter JM, Moore PK. Text book of pharmacology, vol 5. New York: Churchill Livingstone; 2005. p. 666–7.Google Scholar
  13. 13.
    Ravinder P, Vanishree S, Sujatha S, Kishore Kumar K. Effect of carvedilol on pharmacokinetic and pharmacodynamic of glipizide. Int J Pharm Pharm Sci. 2012;4:212–7.Google Scholar
  14. 14.
    Shivraj N, Chandrashekar M. Pharmacodynamic and pharmacokinetic drug interaction of glimepiride and irbesartan in animal models. Int J Phytopharmacol. 2013;4(3):174–8.Google Scholar
  15. 15.
    Sujata V. Pharmacokinetics of the oral direct rennin inhibitor Aliskiren alone and in combination with Irbesartan in renal impairment. Clin Pharmacokinet. 2007;46(8):661–75.CrossRefGoogle Scholar
  16. 16.
    Tanaka E. Clinically important drug interactions: role of CYP enzymes. J Clin Pharm Ther. 1998;23(6):403–16.CrossRefPubMedGoogle Scholar
  17. 17.
    Utpal N, Sanmoy K, Anjan D, Balaram G, Aswathi P, Nilendra C, Tapan P. Pharmacokinetics pharmacodynamics and toxicity of a combination of metoprolol succinate and telmisartan in Wistar albino rats: safety profiling. Regul Toxicol Pharmacol. 2013;65:68–78.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Adepu Anusha
    • 1
  • Dudhipala Narendar
    • 2
  • Boini Krishna Murthy
    • 3
  • Puchchakayala Goverdhan
    • 1
    Email author
  1. 1.Laboratory of Pharmacokinetics and Toxicokinetics, Department of PharmacologyVaagdevi College of Pharmacy, Kakatiya UniversityWarangalIndia
  2. 2.Department of PharmaceuticsVaagdevi Institute of Pharmaceutical SciencesWarangalIndia
  3. 3.Department of Pharmacological and Pharmaceutical SciencesCollege of Pharmacy, University of HoustonHoustonUSA

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