Skip to main content
SpringerLink
Log in

In vitro amiodarone protein binding and its interaction with warfarin

  • Published:
Experientia Aims and scope Submit manuscript

Summary

The binding of amiodarone to human plasma protein and to bovine serum, albumin was studied by three different methods, ultracentrifugation, equilibrium dialysis and fluorescence spectroscopy. The fraction of amiodarone bound to plasma protein amounted to 96.3%. The changes in the binding properties of 1-anilino-naphthalene-8-sulfonate for bovine serum albumin using warfarin and amiodarone as independent inhibitors were analyzed in terms of binding site specificity. The findings indicated that amiodarone and warfarin have two different binding sites on bovine serum albumin, so a noncompetitive inhibition mechanism was indicated. On the basis of our data we cannot exclude other mechanisms of interaction besides direct displacement of one drug by another; nevertheless, metabolite interference between amiodarone and coagulation cofactors may better explain the enhancement of warfarin's pharmacological action in association with amiodarone.

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. Rosenbaum, M. B., Chiale, P. A., Halpern, M. S., Nau, G. J., Przybylski, J., Levi, R. J., Lazzari, J. O., and Elizari, M. V., Am. J. Cardiol.38 (1976) 934.

    Article  CAS  PubMed  Google Scholar 

  2. Heger, J. J., Prystowsky, E. N., Jackman, W. M., Naccarelli, G. V., Warfel, K. A., Rinkenberger, R. L., and Zipes, D. P., New Engl. J. Med.305 (1981) 539.

    Article  CAS  PubMed  Google Scholar 

  3. Marcus, F. I., Fontaine, G. H., Frank, R., and Grosgogeat, Y., Am. Heart J.101 (1981) 480.

    Article  CAS  PubMed  Google Scholar 

  4. Latini, R., Tognoni, G., and Kates, R. E., Clin. Pharmacokinet.9 (1984) 136.

    Article  CAS  PubMed  Google Scholar 

  5. Kannan, R., Nademanee, K., Hendrickson, J. A., Rostami, H. J., and Singh, B. N., Clin. Pharmac. Ther.31 (1982) 438.

    Article  CAS  Google Scholar 

  6. Storey, G. C. A., Adams, P. C., Nicholson, M. R., Campbell, R. W. F., and Holt, D. W., Br. J. clin. Pharmac.15 (1983) 148P.

    Google Scholar 

  7. Harris, L., McKenna, W. J., Rowland, E., Holt, D. W., Storey, G. C. A., and Krikler, D. M., Circulation67 (1983) 45.

    Article  CAS  PubMed  Google Scholar 

  8. Beck-Peccoz, P., Piscitelli, G., Volpi, A., Maggioni, A. P., Cattaneo, M. G., Giani, P., Landolina, M., Tognoni, G., and Faglia, G., in: Proc. Meeting Thyroid Disorders Associated with Iodine Deficiency and Excess, Freiburg, 24–26 April 1984.

  9. Rees, A., Dalal, J. J., Reid, P. G., Henderson, A. H., and Lewis, M. J., Br. med. J.282 (1981) 1756.

    Article  CAS  Google Scholar 

  10. Hamer, A., Peter, T., Mandel W. J., Scheinman, M. M., and Weiss, D., Circulation65 (1982) 1025.

    Article  CAS  PubMed  Google Scholar 

  11. Riva, E., Gerna, M., Latini, R., Giani, P., Volpi, A., and Maggioni, A., J. cardiovasc. Pharmac.4 (1982) 264.

    Article  CAS  Google Scholar 

  12. Aarons, L., Clifton, P., Fleming, G., and Rowland, M., J. Pharm. Pharmac.32 (1980) 537.

    Article  CAS  Google Scholar 

  13. Weder, H. G., Schildknecht, J., and Kesselring, P., Am. Lab.10 (1971) 15.

    Google Scholar 

  14. Weber, G., and You, L. B., J. biol. Chem.239 (1964) 1415.

    Article  CAS  PubMed  Google Scholar 

  15. Andreasen, F., Agerbaek, H., Bjerregaard, P., and Gøtzsche, H., Eur. J. clin. Pharmac.19 (1981) 293.

    Article  CAS  Google Scholar 

  16. Bonati, M., Gaspari, F., D'Aranno, E., Benfenati, E., Neyroz, P., Galletti, F., and Tognoni, G., J. pharm. Sci.73 (1984) 829.

    Article  CAS  PubMed  Google Scholar 

  17. Bonati, M., Gohlke, J. R., and Rao, D. S., Biochemistry6 (1967) 3510.

    Article  Google Scholar 

  18. Stryer, L., J. molec. Pharmac.13 (1965) 482.

    CAS  Google Scholar 

  19. Scatchard, G., Ann. N. Y. Acad. Sci.51 (1949) 660.

    Article  CAS  Google Scholar 

  20. Klotz, I. M., Triwush, H., and Walker, F. M., J. Am. chem. Soc.70 (1948) 2935.

    Article  CAS  PubMed  Google Scholar 

  21. Jun, H. W., Luzzi, L. A., and Hsu, P. L., J. pharm. Sci.61 (1972) 1835.

    Article  CAS  PubMed  Google Scholar 

  22. Serlin, M. J., Sibeon, R. G., and Green, G. J., Br. med. J.283 (1981) 58.

    Article  CAS  Google Scholar 

  23. Richard, C., Riou, B., Fournier, C., Rimailho, A., and Auzèpy, P., Circulation68, suppl. III (1983) A1122.

    Google Scholar 

Download references

Author information

Author notes

  1. P. Neyroz

    Present address: Dept. Biology, Johns Hopkins University, 21218, Baltimore, Md, USA

Authors and Affiliations

  1. Laboratory of Clinical Pharmacology, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Via Eritrea, 62, I-20157, Milan, Italy

    P. Neyroz & M. Bonati

Authors
  1. P. Neyroz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Bonati
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was partially funded by the CNR (National Research Council, Rome, Italy), Program on Clinical Pharmacology and Rare Diseases. The authors would like to thanks Drs E. Marzi and E. riva for their help.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Neyroz, P., Bonati, M. In vitro amiodarone protein binding and its interaction with warfarin. Experientia 41, 361–363 (1985). https://doi.org/10.1007/BF02004505

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02004505

Key words

Search

Navigation