Skip to main content
SpringerLink
Log in

Effect of adjuvant arthritis on the disposition of acebutolol enantiomers in rats

  • Inflammation and Immunomodulation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

Disease states such as arthritis may interact with the kinetics of β-blockers. Acebutolol (AC) is a chiral β-blocker which is available as a racemate. The beneficial properties of AC, however, is attributed mainly to theS-(+)-enantiomer. The disposition of AC enantiomers and their active, chiral metabolites, diacetolol (DC) were examined after oral administration to healthy and adjuvant-induced arthritic (AA) female Sprague-Dawley rats. Arthritis was induced by tail base injection ofMycobacterium butyricum. Swelling of hind and forepaws were apparent in 10–16 days in AA but not controls. Control and AA rats were sacrificed at 0.5, 1, 2, 4, 6 and 8 h after a 25 mg/kg oral AC dose and blood was collected (n=6). Significant three to tenfold increases in the initial plasma concentrations (0.5–2h) of AC were observed in AA. Enantiomers were equally affected, thus ACS∶R ratio was not changed. Higher plasma concentrations of the metabolite were only significant at 2h. The ratio of DC∶AC, however, was unaffected by AA. The DCS∶R ratio was significantly decreased at 0.5 and 1 h in AA. The limited protein binding of AC (10%) was neither stereoselective nor affected by AA. Reduced intrinsic clearance in AA may be responsible for these observations.

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. E. D. Harris,Rheumatoid arthritis: the clinical spectrum. InTextbook of Rheumatology. (Eds. W. N. Kelly, E. D. Harris, S. Ruddy, et al.) pp. 928–963, WB Saunders, Philadelphia 1981.

    Google Scholar 

  2. F. M. Belpaire, M. G. Bogeart and M. Rosseneu,Binding of β-adrenoceptor blocking drugs to human serum albumin, to al-acid glycoprotein and to human serum. Eur. J. Clin. Pharmacol.22, 253–256 (1982).

    PubMed  Google Scholar 

  3. T. Walle, J. G. Webb, E. E. Bagwell, K. Halle, H. B. Daniell and T. E. Gaffney,Stereoselective delivery and actions of beta receptor antagonists. Biochem. Pharmacol.,37, 115–124 (1988).

    PubMed  Google Scholar 

  4. F. Jamali, R. Mehvar and F. M. Pasutto,Enantioselective aspects of drug action and disposition: Therapeutic pitfalls. J. Pharm. Sci.78, 695–715 (1989).

    PubMed  Google Scholar 

  5. M. W. Whitehouse,Adjuvant-induced polyarthritis in rats. InHandbook of Animal Models for the Rheumatic Diseases. Vol I. (Eds. R. Greenwald and H. Diamond) pp. 3–16. CRC Press, Boca Raton, Florida 1988.

    Google Scholar 

  6. H. Bishop, R. E. Schneider and P. Welling,Plasma propranolol concentrations in rats with adjuvant-induced arthritis. Biopharm. Drug Dispos.2, 291–297 (1981).

    PubMed  Google Scholar 

  7. K. A. Walker, H. E. Barber and G. M. Hawksworth,Mechanism responsible for altered propranolol disposition in adjuvant-induced arthritis in the rat. Drug Metab. Dispos.14, 482–486 (1986).

    PubMed  Google Scholar 

  8. F. M. Belpaire, F. De Smet, B. Chindavijak, N. Fraeyman and M. G. Bogaert,Effect of turpentine-induced inflammation on the disposition kinetics of propranolol, metoprolol, and antipyrine in the rat. Fundam. Clin. Pharmacol.3, 79–88 (1989).

    PubMed  Google Scholar 

  9. B. Chindavijak, F. M. Belpaire, F. De Smet and M. G. Bogaert,Alteration of the pharmacokinetics and metabolism of propranolol and antipyrine elicited by indwelling catheters in the rat. J. Pharmacol. Exp. Ther.246, 1075–1079 (1988).

    PubMed  Google Scholar 

  10. M. Yauhara, J. Fujiwara, S. Kitade, H. Katayama, K. Okumura and R. Hori,Effect of altered plasma protein on pharmacokinetics and pharmacodynamics of propranolol in rats after surgery. J. Pharmacol. Exp. Ther.235, 513–520 (1985).

    PubMed  Google Scholar 

  11. A. Roux, B. Flouvat, Y. Fouache and J. P. Bourdarias,Systemic bioavailability of acebutolol in man. Biopharm. Drug Dispos.4, 293–297 (1983).

    PubMed  Google Scholar 

  12. T. J. Coombs, C. J. Coulson and V. J. Smith,Blood plasma binding of acebutolol and diacetolol in man. Br. J. Clin. Pharmac.9, 395–397 (1980).

    Google Scholar 

  13. M. Piquette-Miller, R. T. Foster, C. T. Kappagoda and F. Jamali,Pharmacokinetics of acebutolol enantiomers in man. J. Pharm. Sci.80, 313–316 (1991).

    PubMed  Google Scholar 

  14. M. Piquette-Miller, R. T. Foster, F. M. Pasutto and F. Jamali,Stereospecific high-performance liquid chromographic assay of acebutolol in human plasma and urine. J. Chromatogr.526, 129–137 (1990).

    PubMed  Google Scholar 

  15. M. Piquette-Miller and R. T. Foster,Stereospecific HPLC assay of diacetolol. J. Chromatogr.533, 300–303 (1990).

    PubMed  Google Scholar 

  16. R. F. Collins and C. F. George,Studies on the disposition and fate of [14 C]-acebutolol in man and dog. Br. J. Clin. Pharmacol.3, 346P (1975).

  17. P. J. Meffin, R. A. Winkle, F. A. Peters and D. C. Harrison,Dose-dependent acebutolol dispostion after oral administration. Clin. Pharmacol. Ther.24, 542–547 (1978).

    PubMed  Google Scholar 

  18. M. Piquette-Miller, R. T. Foster, C. T. Kappagoda and F. Jamali,Effect of aging on the pharmacokinetics of acebutolol enantiomers. J. Clin. Pharmacol.32, 148–156 (1992).

    PubMed  Google Scholar 

  19. R. E. Schneider, H. Bishop, M. J. Kendall and C. P. Quarternan,Effect of inflammatory disease on plasma concentrations of three β-adrenoceptor blocking agents. Int. J. Clin. Pharmacol. Ther. Tox.19, 158–162 (1981).

    Google Scholar 

  20. H. Mielants et al.Intestinal mucosal permeability in inflammatory rheumatic diseases. II. Role of disease. J. Rheumatology18, 394–400 (1991).

    Google Scholar 

  21. R. Gabriel, C. M. Kaye and M. G. Sankey,Preliminary observations on the excertion of acebutolol and its acetyl metabolite in the urine and faeces of man. J. Pharm. Pharmacol.33, 386–387 (1981).

    PubMed  Google Scholar 

  22. B. J. Key, C. A. Mucklow and H. Bishop,The absorption of propranolol from the jejunum in rats with adjuvant-induced arthritis. Biopharm. Drug Dispos.7, 233–237 (1986).

    PubMed  Google Scholar 

  23. C. F. George and B. S. Gruchy,Elimination of drugs by active intestinal transport. J. Pharm. Pharmacol.31, 643–644 (1979).

    PubMed  Google Scholar 

  24. B. Chindavijak, F. M. Belpaire and M. G. Bogaert,In-vitro biotransformation of antipyrine, lignocaine and propranolol in the liver of rats with turpentine-induced inflammation. J. Pharm. Pharmacol.39, 883–886 (1987).

    PubMed  Google Scholar 

  25. B. D. Andresen and F. T. Davis,Metabolism of acebutolold 6 in the rat correlates with the identification of a new metabolite in human urine. Drug Metab. Dispos.79, 360–365 (1979).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, T6G 2N8, Edmonton, Alberta, Canada

    M. Piquette-Miller &  F. Jamali

Authors
  1. M. Piquette-Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Jamali
    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

Piquette-Miller, M., Jamali, F. Effect of adjuvant arthritis on the disposition of acebutolol enantiomers in rats. Agents and Actions 37, 290–296 (1992). https://doi.org/10.1007/BF02028122

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02028122

Keywords

Search

Navigation