Skip to main content
SpringerLink
Log in

Aminoglutethimide and warfarin

A new important drug interaction

  • Original Articles
  • Aminoglutethimide, Warfarin, Interaction
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

Aminoglutethimide (AG) has recently been introduced for endocrine therapy in patients with advanced breast and endometrial cancer. In this study two patients being treated with both AG and the anticoagulant agent warfarin are described. An important drug interaction was observed, resulting in a decrease in the anticoagulant effect of warfarin. This was shown by means of thrombotest measurements and pharmacokinetic evaluation of warfarin. A 3- to 5-fold increase in warfarin clearance was found.

This interaction is probably due to an AG-promoted induction of hepatic microsomal enzymes accelerating warfarin metabolism.

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. Andreasen PB, Vesell ES (1974) Comparison of plasma levels of antipyrine, tolbutamide, and warfarin after oral and intravenous administration. Clin Pharmacol Ther 16: 1059–1065

    Google Scholar 

  2. Bachmann K, Shapiro R (1977) Protein binding of coumarin anticoagulants in disease states. Clin Pharmacokinet 2: 110–126

    Google Scholar 

  3. Bjornsson TD, Blachke TF, Meffin PJ (1977) High-pressure liquid chromatography analysis of drugs in biological fluids. I. Warfarin. J Pharm Sci 66: 142–149

    Google Scholar 

  4. Breckenridge A, Orme M (1973) Kinetics of warfarin absorption in man. Clin Pharmacol Ther 14: 955–961

    Google Scholar 

  5. Breckenridge A, Orme M, Wesseling H, Lewis RJ, Gibbons R (1974) Pharmacokinetics and pharmacodynamics of the enantiomers of warfarin in man. Clin Pharmacol Ther 15: 424–430

    Google Scholar 

  6. Bruning PF, van Loon J, Donker M, Bonfrèr JGM (1983) Pros and cons of aminoglutethimide for advanced postmenopausal breast cancer. Abstracts, EORTC and Breast Cancer Cooperative Group, p IX.25

  7. Corn M (1966) Effect of phenobarbital and glutethimide on biological half-life of warfarin. Thromb Diathes Haemorrh 16: 606–612

    Google Scholar 

  8. Gilette J (1973) Overview of drug-protein binding. Ann NY Acad Sci 226: 6–29

    Google Scholar 

  9. Jackson L, Homeida M, Roberts CJC (1978) The features of hepatic enzyme induction with glutethimide in man. Br J Clin Pharmacol 6: 525–528

    Google Scholar 

  10. MacDonald MG, Robinson DS, Sylwester D, Jaffe JJ (1969) The effect of phenobarbital, chloral betaine, and glutethimide administration on warfarin plasma levels and hypoprothrombinemic responses in man. Clin Pharmacol Ther 10: 80–84

    Google Scholar 

  11. Murray FT, Santner S, Samojlik E, Santen RJ (1979) Serum aminoglutethimide levels: studies of serum half-life, clearance and patient compliance. J Clin Pharmacol 19: 704–711

    Google Scholar 

  12. Murray RML, Pitt P, Jerums G (1981) Medical adrenalectomy with aminoglutethimide in the management of advanced breast cancer. Med J Aust 1: 179–181

    Google Scholar 

  13. O'Reilly R, Welling P, Wagner J (1971) Pharmacokinetics of warfarin following intravenous administration to man. Thromb Diathes Haemorrh 25: 178–186

    Google Scholar 

  14. Quinn MA, Campbell JJ, Murray R, Pepperell RJ (1981) Tamoxifen and aminoglutethimide in the management of patients with advanced endometrial carcinoma not responsive to medroxyprogesterone. Aust NZ J Obstet Gynaecol 21: 226–229

    Google Scholar 

  15. Santen RJ, Brodie AMH (1982) Suppression of oestrogen production as treatment of breast carcinoma: pharmacological and clinical studies with aromatase inhibitors. Clin Oncol 1: 77–93

    Google Scholar 

  16. Santen RJ, Samojlik E (1979) Medical adrenalectomy for treatment of metastatic breast carcinoma. In: McGuire WL (ed) Breast cancer, vol 3. Plenum, New York, pp 79–115

    Google Scholar 

  17. Santen RJ, Lipton A, Kendall J (1974) Successful medical adrenalectomy with aminoglutethimide. Role of altered drug metabolism. JAMA 230: 1661–1665

    Google Scholar 

  18. Santen RJ, Worgul TJ, Samojlik E, Interrante A, Boucher AE, Lipton A, Harvey HA, White DS, Smart E, Cox C, Wells SA (1981) Randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast carcinoma. N Engl J Med 305: 545–551

    Google Scholar 

  19. Thompson TA, Vermeulen JD, Wagner WE Jr, Le Sher AR (1981) Aminoglutethimide bioavailability, pharmacokinetics and binding to blood constituents. J Pharm Sci 70: 1040–1043

    Google Scholar 

  20. Vessel ES, Shively CA (1974) Liquid chromatography assay of warfarin: similarity of warfarin half-lives in human subjects. Science 184: 466–468

    Google Scholar 

  21. Welle-Vatne, A, Jahren G (1980) Analysis of warfarin in plasma by high-performance liquid chromatography. Medd Norsk Farm Selskap 42: 45–52

    Google Scholar 

  22. Wilkinson GR, Shand DG (1974) A physiologic approach to hepatic drug clearance. Clin Pharmacol Ther 18: 377–390

    Google Scholar 

  23. Yacobi A, Udall J, Levy G (1976) Serum protein binding as a determinant of warfarin body clearance and anticoagulant effect. Clin Pharmacol Ther 19: 552–558

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, University of Bergen, Bergen, Norway

    Per Eystein Lønning & Stener Kvinnsland

  2. Pharmaceutical Development Department, Nyegaard & Co A/S, Oslo, Norway

    Grete Jahren

Authors
  1. Per Eystein Lønning
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stener Kvinnsland
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Grete Jahren
    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

Lønning, P.E., Kvinnsland, S. & Jahren, G. Aminoglutethimide and warfarin. Cancer Chemother. Pharmacol. 12, 10–12 (1984). https://doi.org/10.1007/BF00255901

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00255901

Keywords

Search

Navigation