Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

The effect of sulphinpyrazone on oxidative drug metabolism in man: Inhibition of tolbutamide elimination

  • 37 Accesses

  • 43 Citations


The effect of sulphinpyrazone on tolbutamide elimination was investigated in 6 healthy male volunteers. Co-administration of sulphinpyrazone (200 mg, 6 hourly) reduced mean plasma tolbutamide clearance by 40% and prolonged mean tolbutamide half-life by 80%. Twenty four hours after the cessation of a one week period of chronic sulphinpyrazone therapy tolbutamide plasma clearance (30% reduction) and half-life (19% prolongation) were still significantly different to control values, even though sulphinpyrazone could not be detected in the plasma of any of the subjects at this time. In vitro studies of the plasma protein binding of tolbutamide demonstrated concentration dependent binding but displacement of tolbutamide by sulphinpyrazone in vitro only became apparent at high concentrations of added sulphinpyrazone. Although the concentration dependence of tolbutamide protein binding demonstrated in vitro was also observed in the subject plasma samples, the magnitude of this effect was small. It is concluded that sulphinpyrazone and its metabolite(s) decrease the plasma clearance of tolbutamide by inhibition of oxidative metabolism.

This is a preview of subscription content, log in to check access.


  1. 1.

    Margulies EH, White AM, Sherry S (1980) Sulphinpyrazone: A review of its pharmacological properties and therapeutic uses. Drugs 20: 179–197

  2. 2.

    Davis JW, Johns LE (1978) Possible interaction of sulphinpyrazone with coumarins. N Engl J Med 299–955

  3. 3.

    Gallus A, Birkett DJ (1980) Sulphinpyrazone and warfarin: a probable drug interaction. Lancet 1: 535–536

  4. 4.

    Weiss M (1979) Potentiation of coumarin effect by sulphinpyrazone. Lancet 1: 609

  5. 5.

    Thompson PL, Serjeant C (1981) Potentially serious interaction of warfarin with sulphinpyrazone. Med J Aust 1: 41

  6. 6.

    Miners JO, Foenander T, Wanwimolruk S, Gallus AS, Birkett DJ (1982) Interaction of sulphinpyrazone with warfarin. Eur J Clin Pharmacol 22: 327–331

  7. 7.

    Lewis RJ, Trager WF, Chan KF, Breckenridge A, Orme M, Rowland M, Schary W (1974) Warfarin: Stereochemical aspects of its metabolism and the interaction with phenylbutazone. J Clin Invest 53: 1607–1617

  8. 8.

    Pond SM, Birkett DJ, Wade DN (1977) Mechanisms of inhibition of tolbutamide metabolism: phenylbutazone, oxyphenbutazone, sulphaphenazole. Clin Pharmacol Ther 22: 573–579

  9. 9.

    Nation RL, Peng GW, Chiou WL (1978) Simple, rapid and micro high-pressure liquid chromatographic method for the simultaneous determination of tolbutamide and carboxytolbutamide in plasma. J Chromatogr 146: 121–131

  10. 10.

    Benet LZ, Galeazzi RL (1979) Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci 68: 1071–1074

  11. 11.

    O'Reilly RA (1980) Stereoselective interaction of trimethoprimsulfamethoxazole with the separated enantiomorphs of racemic warfarin in man. N Engl J Med 302: 33–35

  12. 12.

    O'Reilly RA (1976) The stereoselective interaction of warfarin and metronidazole in man. N Engl J Med 295: 354–357

  13. 13.

    Thomas RC, Ikeda GJ (1966) The metabolic fate of tolbutamide in man and rat. J Med Chem 9: 507–510

  14. 14.

    Nelson E, O'Reilly I (1961) Kinetics of carboxytolbutamide excretion following tolbutamide and carboxytolbutamide administration. J Pharmacol Exp Ther 132: 103–109

  15. 15.

    Kirstein Pedersen A, Jakobsen P (1981) Sulphinpyrazone metabolism during long-term therapy. Br J Clin Pharmacol 11: 597–603

  16. 16.

    Christensen LK, Hansen JM, Kristensen M (1963) Sulphaphenazole-induced hypoglycaemic attacks in tolbutamide-treated diabetics. Lancet 2: 1298–1301

  17. 17.

    Skovsted L, Hansen JM, Kristensen M, Christensen LK (1974) Inhibition of drug metabolism in man. In: Morselli PL, Garattini S, Cohen SN (eds) Drug interactions. Raven Press, New York, pp 81–90

  18. 18.

    Hansen JM, Busk G, Niemi G, Haase NJ, Lumholtz B, Skovsted L, Kampmann JP (1980) Inhibition of phenytoin metabolism by sulfinpyrazone. World Conference on Clinical Pharmacology and Therapeutics (London), Abstract No. 0584

  19. 19.

    Walter E, Staiger Ch, de Vries J, Zimmermann R, Weber E (1981) Induction of drug metabolising enzymes by sulfinpyrazone. Eur J Clin Pharmacol 19: 353–358

  20. 20.

    Chen W, Vrindten PA, Dayton PG, Burns JJ (1962). Accelerated aminopyrine metabolism in human subjects. Life Sci 2: 35–42

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Miners, J.O., Foenander, T., Wanwimolruk, S. et al. The effect of sulphinpyrazone on oxidative drug metabolism in man: Inhibition of tolbutamide elimination. Eur J Clin Pharmacol 22, 321–326 (1982).

Download citation

Key words

  • sulphinpyrazone
  • tolbutamide
  • drug metabolism
  • drug interaction
  • protein binding
  • elimination of tolbutamide