Skip to main content
SpringerLink
Log in

Increased sensitivity to phenprocoumon during methyltestosterone therapy

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

Abnormal sensitivity to phenprocoumon in a castrated male who was receiving substitution therapy with methyltestosterone, has been studied and compared with pharmacokinetic data obtained from six control subjects, all of whom had cardiac disorders. The concentration-effect relationship for phenprocoumon in the castrated patient was evaluated by the mathematical model described by Nagashima et al. (1969). The possible mechanisms involved in sensitization by methyltestosterone of the response to phenprocoumon are discussed. It is suggested that methyltestosterone increases the affinity of the receptor sites in the liver for phenprocoumon, an effect which has previously been attributed to other C17-alkyl-substituted androgens.

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. Allington, M.J.: Owren's method for the control of anticoagulant therapy. J. clin. Path.11, 62–68 (1958)

    Google Scholar 

  2. Andreasen, F.: Protein binding of drugs in plasma from patients with acute renal failure. Acta pharmacol. (Kbh.)32, 417–429 (1973)

    Google Scholar 

  3. Chriske, H.W., Smekal, P.V., Knabe, M., Kray, D.: Pharmakokinetische Untersuchungen bei erhöhter Ansprechbarkeit gegenüber Phenprocoumon (Marcoumar®). Med. Welt (Stuttg.)24, 1620–1621 (1973 a)

    Google Scholar 

  4. Chriske, H.W., Gross, R., Hilger, H.H., Oette, K., Smekal, P.V., Knabe, M., Kray, D.: Pharmakokinetische Untersuchungen zur Phenprocoumon (Marcoumar®)-Resistenz. Verh. dtsch. Ges. inn. Med.79, 1311–1314 (1973 b)

    Google Scholar 

  5. Coon, W.W., Willis, P.W.: Some aspects of the pharmacology of oral anticoagulants. Clin. Pharmacol. Ther.11, 312–336 (1970)

    Google Scholar 

  6. Dresdale, F.C., Hayes, J.C.: Potential dangers in the combined use of methandrostenolone and sodium warfarin. J. med. Soc. N.J.64, 609–612 (1967)

    Google Scholar 

  7. Eipe, J.: Drugs affecting therapy with anticoagulants. Med. Clin. North Amer.56, 255–262 (1972)

    Google Scholar 

  8. Foged, L., Husted, S., Andreasen, F.: Reduced binding of phenprocoumon (Marcoumar®) to HSA in the presence of furosemid. Acta pharmacol. (Kbh.)

  9. Formiller, M., Cohon, M.S.: Coumarin and indandione anticoagulants. Potentiators and antagonists. Amer. J. Hosp. Pharm.26, 574–582 (1969)

    Google Scholar 

  10. Furman, R.H., Howard, R.P., Alaupovic, P.: Reduction in serum lipid levels during oral administration of C17-alkylated steroids, methyltestosterone and methylandrostanopyrazole, to hyperlipemic subjects. J. Lab. clin. Med.60, 876 (1962)

    Google Scholar 

  11. Gugler, R.: Beeinflussung der Wirkung oraler Antikoagulantien durch andere Pharmaka. Med. Welt (Stuttg.)25, 12–15 (1974)

    Google Scholar 

  12. Koch-Weser, J., Sellers, E.M.: Drug interactions with coumarin anticoagulants. New Engl. J. Med.285, 487–498 and 547 – 559 (1971)

    Google Scholar 

  13. Levy, G.: Relationship between rate of elimination of tubocurarine and rate of decline of its pharmacologic activity. Brit. J. Anaesth.36, 694–695 (1964)

    Google Scholar 

  14. Levy, G.: Kinetics of pharmacologic effects. Clin. Pharmacol. Ther.7, 362–372 (1966)

    Google Scholar 

  15. Levy, G.: Kinetics of pharmacologic activity of succinylcholine in man. J. pharm. Sci.56, 1687–1688 (1967)

    Google Scholar 

  16. Levy, G.: Pharmacokinetics of succinylcholine in newborns. Anesthesiol.32, 551–552 (1970)

    Google Scholar 

  17. Levy, G., O'Reilly, R.A., Aggeler, P.M., Keech, G.M.: Pharmacokinetic analysis of the effect of barbiturates on the anticoagulant action of warfarin in man. Clin. Pharmacol. Ther.11, 372–377 (1970)

    Google Scholar 

  18. Levy, G.: Comparative pharmacokinetics of the anticoagulant effect of coumarin drugs in man and rat. J. Pharmacokinet. Biopharm.1, 541–551 (1973)

    Google Scholar 

  19. Lowenthal, J., MacFarlane, J.A.: The nature of the antagonism between vitamin-K and in-direct anticoagulants. J. Pharmacol. exp. Ther.143, 273–277 (1964)

    Google Scholar 

  20. Marquardt, G.H., Fischer, C.I., Levy, P., Dowben, R.M.: Effect of anabolic steroids on liver function tests and creatinine excretion. J. Amer. med. Ass.175, 851–853, (1961)

    Google Scholar 

  21. Murakami, M., Odake, K., Matsuda, T., Onchi, K., Umeda, T., Nishino, T.: Effects of anabolic steroids on anticoagulant requirements. Jap. Circulat. J. (En.)29, 243–250 (1965)

    Google Scholar 

  22. Nagashima, R., O'Reilly, R.A., Levy, G.: Kinetics of pharmacologic effects in man: The anticoagulant action of warfarin. Clin. Pharmacol. Ther.10, 22–35 (1969)

    Google Scholar 

  23. O'Reilly, R.A., Aggeler, P.M.: Determinants of the response to oral anticoagulant drugs in man. Pharmacol. Rev.22, 35–96 (1970)

    Google Scholar 

  24. O'Reilly, R.A., Aggeler, P.M., Hoag, M.S., Leong, L.S., Kropatkin, M.L.: Heriditary transmission of exceptional resistance to coumarin anticoagulant drugs. The first reported kindred. New Engl. J. Med.271, 809–815 (1964)

    Google Scholar 

  25. O'Reilly, R.A., Levy, G.: Pharmacokinetic analyses of potentiating effect of phenylbutazone on anticoagulant action of warfarin in man. J. pharm. Sci.59, 1258–1261 (1970 a)

    Google Scholar 

  26. O'Reilly, R.A., Levy, G.: Kinetics of the anticoagulant effect of bishydroxycoumarin in man. Clin. Pharmacol. Ther.11, 378–384 (1970 b)

    Google Scholar 

  27. Pliska, V.: On the in vivo kinetics of drug action. Arzneimittel-Forsch.16, 886–893 (1966)

    Google Scholar 

  28. Pyörälä, K., Kekki, M.: Decreased anticoagulant tolerance during methandrostenolone therapy. Scand. J. clin. Lab. Invest.15, 367–374 (1963)

    Google Scholar 

  29. Pyörälä, K., Myllylä, G., Kekki, M.: Metabolism of warfarin during methandrostenolone treatment. Ann. Med. exp. Fenn.43, 95–97 (1965)

    Google Scholar 

  30. Raheja, K.L., Reber, E.F., Anderson, D.L.: Effect of vitamin K3 and testosterone propionate on plasma cholesterol level and prothrombin rate in castrated and intact rats. Indian J. Physiol. Pharmacol.15, 143–150 (1971)

    Google Scholar 

  31. Schrogie, J.J., Solomon, H.M.: The anticoagulant response to bishydroxycoumarin. II. The effect of D-thyroxine, clofibrate and norethandrolene. Clin. Pharmacol. Ther.8, 70–77 (1967)

    Google Scholar 

  32. Seiler, K., Duckert, F.: Properties of 3-(1-phenyl-propyl)-4-oxycoumarin (Marcoumar®) in the plasma when tested in normal cases and under the influence of drugs. Thrombos. Diathes. haemorrh. (Stuttg.)19, 389–396 (1968)

    Google Scholar 

  33. Solomon, H.M., Schrogie, J.J.: The anticoagulant response to bishydroxycoumarin. I. The role of individual variation. Clin. Pharmacol. Ther.8, 65–69 (1967 a)

    Google Scholar 

  34. Solomon, H.M., Schrogie, J.J.: Change in receptor affinity: A proposed explanation for the potentiation effect of D-thyroxine on the anticoagulant response to warfarin. Clin. Pharmacol. Ther.8, 797–799 (1967 b)

    Google Scholar 

  35. Stenbjerg, S., Husted, S., Mygind, K.: A circulation factor V inhibitor: Possible side effect of treatment with streptomycin. Scand. J. Haemat.14, 280–285 (1975)

    Google Scholar 

  36. Toohey, M.: Comparison of Quick's, Owren's, and Ware's techniques for the control of anticoagulant therapy. J. clin Path.11, 56–61 (1958)

    Google Scholar 

  37. Woolf, I.L., Babior, B.M.: Vitamin-K and warfarin: Metabolism, function and interaction. Amer. J. Med.53, 261–267 (1972)

    Google Scholar 

  38. Wynn, V., Landon, J., Kawerau, E.: Studies of hepatic function during methandienone therapy. Lancet1961 I, 69–75

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pharmacology, University of Aarhus, Aarhus, Denmark

    S. Husted, F. Andreasen & L. Foged

Authors
  1. S. Husted
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Andreasen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Foged
    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

Husted, S., Andreasen, F. & Foged, L. Increased sensitivity to phenprocoumon during methyltestosterone therapy. Eur J Clin Pharmacol 10, 209–216 (1976). https://doi.org/10.1007/BF00558331

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00558331

Key words

Search

Navigation