Skip to main content
SpringerLink
Log in

Pharmacokinetic and pharmacodynamic of irbesartan in renal hypertensive dogs under non-steady-state and steady-state conditions

  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Summary

The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of irbesartan in renal hypertensive dogs under non-steady-state and steady-state conditions using pharmacokinetic-pharrnacodynamic(PK/PD) modeling. Drugs were administered intragastrically to renal hypertensive dogs, plasma drug concentration was determined by HPLC method and Pharmacologic effects, including SBP, DBP, dp/dtmax and LVSP, were measured simultaneously. AT II, Aldosterone (ALD) and Endothelin (ET) were also used as measurement of effect. The PK and PD data were quantitatively analyzed according to the PK/PD model theory. The pharmacokinetic profiles of irbesartan conformed to a two-compartment open model. There was hysteresis loops between effects and plasma concentrations under non-steady-state condition. The relationship between effects and effect compartment concentrations (Ce) could be represented by the Sigmoid-Emax model. The Hysteresis loops disappeared under steady-state condition with more rapidly attainment of maximum concentration and effect. There were certain difference of pharmacokinetic and pharmacodynamic properties between non-steady-state and steady-state condition.

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. Bernard Waeber. (2001): A review of irbesartan in antihypertensive therapy: comparison with other antihypertensive agents. Current Therapeutic Research, 62, 505–521

    Article  CAS  Google Scholar 

  2. Hartmut Derendorf, Bernd Meibohm. (1999): Modeling of Pharmacokinetic/Pharmacodynamic(PK/PD) Relationships: Concepts and Perspectives. Pharmaceutical Research, 16, 176–177

    Article  PubMed  CAS  Google Scholar 

  3. XU Shuyun, BIAN Rulian, CHEN Xiu. (2002): The Methodology of Pharmacological Experiment (Third edition) Beijing: People's Sanitation Press, 950–951

    Google Scholar 

  4. Collum WA. (1981): Simultaneous pharmacokinetics and pharmacodynamics modeling, J Pharmacokinet Biopharm, 9, 367–388

    Article  Google Scholar 

  5. 5.YIN Xiao-xing, ZHANG Yin-di, LUO Jian-ping. (1997): Pharmacokinetic pharmacodynamic modeling of metoprolol stereoisomers in spontaneously hypertensive rat. Acta pharmacological Sinica, 18, 104–108

    Google Scholar 

  6. Meibohm B, Derendorf H. (1997): Basic concepts of pharmacokinetic/pharmacodynamic(PK/PD) Modelling. Int J Clin Pharmacol Ther, 35, 401–413

    PubMed  CAS  Google Scholar 

  7. CHEN Zhi-yang, ZHENG Qing-shan, SUN Rui-yuan. (2002): Introduction to the main functions of DAS pharmacological software. Chinese Journal of Clinical Pharmacology andTherapeutics, 7, 562–564

    Google Scholar 

  8. Greathouse M (2002): A review of olmesartan medoxomil monotherapy: antihypertensive efficacy similar to that of other angiotensin II receptor blocker/hydrochlorothiazide combinations? Congest Heart Fail, 8, 313–320

    Article  PubMed  CAS  Google Scholar 

  9. Rosenstock J, Rossi L, Lin CS, MacNeil D, Osbakken M (1998): The effects of irbesartan added to hydrochlorothiazide for the treatment of hypertension in patients non-responsive to hydrochlorothiazide alone. J Clin Pharm Ther, 23, 433–440

    Article  PubMed  CAS  Google Scholar 

  10. Mancia G. Clinical differences among angiotensin II receptor antagonists (2001): Blood Press Suppl, 2, 19–24

    Article  PubMed  CAS  Google Scholar 

  11. SHI Shao-Jun, CHEN Hui, GU Shi-Fen, ZENG Fan-Dian (2003): Pharmacokinetic pharmacodynamic modeling of daurisoline and dauricine in beagle dogs. Acta pharmacological Sinica, 24, 1011–1015

    Google Scholar 

  12. Fuseau EΘ§Sheiner LB. (1984): Commentary: simultaneous modeling of pharmacokinetics and pharmacodynamics with a nonparametric pharmacodynamic model. Clin Pharmacol Ther, 35, 733–741

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Pharmacy, Anhui Medical University, China Yijishan Hospital, Wannan Medical College, Nanjing, China

    Fu-Rong Qiu

  2. Center of Pharmacokinetics, China Pharmaceutical University, Nanjing, China

    Hai-Tang Xie

  3. College of Pharmacy, Anhui Medical University, 230032, Hefei, China

    Xiao-Hui Huang & Jun Li

Authors
  1. Xiao-Hui Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fu-Rong Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hai-Tang Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Li
    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

Huang, XH., Qiu, FR., Xie, HT. et al. Pharmacokinetic and pharmacodynamic of irbesartan in renal hypertensive dogs under non-steady-state and steady-state conditions. Eur. J. Drug Metab. Pharmacokinet. 30, 121–126 (2005). https://doi.org/10.1007/BF03226417

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03226417

Keywords

Search

Navigation