Clinical Pharmacokinetics

, Volume 11, Issue 5, pp 402–410 | Cite as

Effects of Ischaemic Heart Disease, Crohn’s Disease and Antimicrobial Therapy on the Pharmacokinetics of Sulphinpyrazone

  • H. Andrew Strong
  • Rachel Angus
  • Jonathan Oates
  • Jaspal Sembi
  • Peter Howarth
  • Andrew G. Renwick
  • Charles F. George
Original Research Article

Summary

The renewed interest in sulphinpyrazone in recent years has arisen from its potential to inhibit platelet aggregation. In vivo much of the activity is probably due to the thioether or sulphide metabolite which has a greater potency and a longer half-life than the parent compound. The sulphide metabolite is formed exclusively by the gut microflora in man. The pharmacokinetics of sulphinpyrazone (200mg orally) have been studied, with particular attention to the formation of the sulphide metabolite, in groups of patients who might be expected to show abnormal formation of this active metabolite due to altered delivery of the drug to the lower gut or altered gut flora. Five patients studied 1 month after a myocardial infarction did not differ markedly from young, normal volunteers with respect to either sulphinpyrazone or its metabolite. Crohn’s disease in the quiescent phase did not significantly alter the pharmacokinetics or metabolism of the drug, but 1 patient who had undergone a hemicolectomy formed negligible concentrations of the active metabolite. Antimicrobial therapy produced highly variable results with almost complete suppression of sulphide formation in some subjects but no apparent effect in others.

Keywords

Normal Volunteer Amoxycillin Sulphasalazine Lincomycin Sulfinpyrazone 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ali M, McDonald JWD. Effects of sulphinpyrazone on platelet prostaglandin synthesis and platelet release of serotonin. Journal of Laboratory and Clinical Medicine 89: 868–875, 1977PubMedGoogle Scholar
  2. Anturan Reinfarction Italian Study Group. Sulphinpyrazone in post-myocardial infarction. Lancet 1: 237–242, 1982Google Scholar
  3. Anturane Reinfarction Trial Research Group. Sulphinpyrazone in the prevention of sudden death after myocardial infarction. New England Journal of Medicine 298: 289–295, 1978CrossRefGoogle Scholar
  4. Anturane Reinfarction Trial Research Group. Sulphinpyrazone in the prevention of sudden death after myocardial infarction. New England Journal of Medicine 302: 250–256, 1980CrossRefGoogle Scholar
  5. Azad Khan AK, Truelove SC. Circulating levels of sulphasalazine and its metabolites and their relation to clinical efficacy of the drug in ulcerative colitis. Gut 21: 706–710, 1980PubMedCrossRefGoogle Scholar
  6. Bradbrook ID, John VA, Morrison PJ, Rogers HJ, Spector RG. Pharmacokinetics of single oral doses of sulphinpyrazone and its major metabolites in plasma and urine. British Journal of Clinical Pharmacology 13: 177–185, 1982PubMedCrossRefGoogle Scholar
  7. Burns JJ, Ju TF, Perel JM, Gutman AB, Brodie BB. A potent new uricosuric agent, the sulfoxide metabolite of the phenylbutazone analogue G-25671. Journal of Pharmacology and Experimental Therapeutics 119: 418–426, 1957PubMedGoogle Scholar
  8. Crooks J, Stevenson IH (Eds). Drugs and the elderly: perspectives in geriatric clinical pharmacology, Macmillan Press Ltd, 1979Google Scholar
  9. Del Maschio A, Livio M, Cerletti C, De Gaetano G. Inhibition of human platelet cyclo-oxygenase by sulfinpyrazone and three of its metabolites. European Journal of Clinical Pharmacology 101: 209–214, 1984CrossRefGoogle Scholar
  10. Dieterle W, Faigle JW, Moppert JW. New metabolites of sulphinpyrazone in man. Arzneimittel-Forschung 30: 989–993, 1980PubMedGoogle Scholar
  11. Drasar BS, Hill MJ. Human intestinal flora, Academic Press, New York, 1984Google Scholar
  12. Kampmann J, Hansen JM, Siersbaek-Nielsen K, Laursen H. Effect of some drugs on penicillin half-life in blood. Clinical Pharmacology and Therapeutics 13: 516–519, 1972PubMedGoogle Scholar
  13. Kirstein Pedersen A, Fitzgerald GA. Cyclo-oxygenase inhibition, platelet function and metabolite formation during chronic sulphinpyrazone therapy. Clinical Pharmacology and Therapeutics 37: 36–42, 1985CrossRefGoogle Scholar
  14. Kirstein Pedersen A, Jakobsen P. Sulphinpyrazone metabolism during long-term therapy. British Journal of Clinical Pharmacology 11: 597–603, 1981CrossRefGoogle Scholar
  15. Kucers A, Bennett N (Eds). The use of antibiotics, William Heinemann Medical Books Ltd, London, 1979Google Scholar
  16. Livio M, Villa S, De Gaetano G. Long lasting inhibition of platelet prostaglandin production but normal vascular prostacyclin generation following sulphinpyrazone administration to rats. Journal of Pharmacy and Pharmacology 32: 718–719, 1980PubMedCrossRefGoogle Scholar
  17. Mahony C, Wolfram KM, Nash PV, Bjornsson TD. Kinetics and metabolism of sulphinpyrazone. Clinical Pharmacology and Therapeutics 33: 491–497, 1983PubMedCrossRefGoogle Scholar
  18. O’Malley K (Ed.). Clinical pharmacology and drug treatment in the elderly, Churchill Livingstone, Edinburgh, 1984Google Scholar
  19. Parsons RL. Drug absorption in gastrointestinal disease with particular reference to malabsorption syndromes. Clinical Pharmacokinetics 2: 45–60, 1977PubMedCrossRefGoogle Scholar
  20. Parsons RL, David JA. Gastrointestinal disease and drug absorption. In Prescott & Nimmo (Eds) Drug absorption. Proceedings of the Edinburgh International Conference, pp. 262–277, ADIS Press, Sydney, 1981Google Scholar
  21. Pay GF, Wallis RB, Zelaschi D. A metabolite of sulphinpyrazone that is largely responsible for the effect of the drug on the platelet prostaglandin pathway. Biochemical Society Transactions 8: 727–728, 1980PubMedGoogle Scholar
  22. Perel JM, Dayton PG, Snell MM, Gutman AB. Studies of interactions among drugs in man at the renal level: probenecid and sulfinpyrazone. Clinical Pharmacology and Therapeutics 10: 834–840, 1969PubMedGoogle Scholar
  23. Prescott LF. Clinically important drug interactions. In Avery (Ed.) Drug treatment, 2nd ed., pp. 236–262, ADIS Press, Sydney; Churchill Livingstone, London, 1980Google Scholar
  24. Renwick AG, Evans SP, Sweatman TW, Cumberland J, George CF. The role of the gut flora in the reduction of sulfinpyrazone in the rat. Biochemical Pharmacology 31: 2649–2656, 1982PubMedCrossRefGoogle Scholar
  25. Rosenkranz B, Fischer C, Jakobsen P, Kirstein Pedersen A, Frolich JC. Plasma levels of sulfinpyrazone and two of its metabolites after a single dose and during the steady state. European Journal of Clinical Pharmacology 24: 251–253, 1983CrossRefGoogle Scholar
  26. Schroder H, Lewkonia RM, Price Evans DA. Metabolism of salicylazosulfapyridine in healthy patients and in patients with ulcerative colitis. Clinical Pharmacology and Therapeutics 14: 802–809, 1973PubMedGoogle Scholar
  27. Strong HA, Oates J, Sembi J, Renwick AG, George CF. Role of the gut flora in the reduction of sulfinpyrazone in humans. Journal of Pharmacology and Experimental Therapeutics 230: 726–732, 1984aPubMedGoogle Scholar
  28. Strong HA, Renwick AG, George CF. The site of reduction of sulphinpyrazone in the rabbit. Xenobiotica 14: 815–826, 1984bPubMedCrossRefGoogle Scholar
  29. Toivanen J, Ylikorkola O, Viinikka L. Differential inhibition of platelet thromboxane and lung prostacyclin production by sulphinpyrazone, acetyl salicylic acid and indomethacin by human tissues in vitro. Thrombosis Research 37: 493–502, 1985PubMedCrossRefGoogle Scholar
  30. Van Hees PAM, Tuinte JHM, Van Rossum JM, Van Tongeren JHM. Influence of intestinal transit-time on azo-reduction of salicylazosulphapyridine (salazopyrin). Gut 20: 300–304, 1979PubMedCrossRefGoogle Scholar
  31. Viinikka L, Toivanen J, Ylikorkola O. The effect of prolonged treatment with sulphinpyrazone on thromboxane A2 and prostacyclin in man. British Journal of Clinical Pharmacology 14: 456–458, 1982PubMedCrossRefGoogle Scholar
  32. Westwick J, Webb H, Lewis GP. The effect of sulphinpyrazone, aspirin and their metabolites on prostacyclin production by rabbit aortic rings. Thrombosis and Haemostasis 42: 99, 1979Google Scholar

Copyright information

© ADIS Press Limited 1986

Authors and Affiliations

  • H. Andrew Strong
    • 1
  • Rachel Angus
    • 1
  • Jonathan Oates
    • 1
  • Jaspal Sembi
    • 1
  • Peter Howarth
    • 1
  • Andrew G. Renwick
    • 1
  • Charles F. George
    • 1
  1. 1.Clinical Pharmacology GroupUniversity of SouthamptonSouthamptonEngland

Personalised recommendations