Summary
Sulphinpyrazone decreases the plasma clearance of tolbutamide and S-warfarin and increases the clearance of R-warfarin, theophylline and antipyrine. In order to determine whether sulphinpyrazone is an inducer or inhibitor or both of oxidative drug metabolism, antipyrine and its metabolites as well as 6-beta-hydroxycortisol were measured in urine before, 24 h and after 23 days of chronic administration of sulphinpyrazone (4×200 mg/day). During chronic treatment sulphinpyrazone increased the ratio of 6-beta-hydroxycortisol to the 17-hydroxycorticosteroids by 70% (p<0.02). The renal clearance of the main oxidative metabolites of antipyrine (4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine) were increased after sulphinpyrazone (p<0.02). Except for norantipyrine, no change in total excretion of antipyrine and its metabolites occurred after 24 h or after 23 days. It is concluded that sulphinpyrazone induces the enzymes which metabolize antipyrine and cortisol.
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Birkett DJ, Miners JO, Gallus A, Attwood J, Wanwimolruk S (1982) Sulphinpyrazone can inhibit or induce drug metabolism: effects on tolbutaminde and theophylline metabolism in man. Br J Clin Pharmacol 14 (4): 574p
Blakely JA, Gent M (1975) Platelets, drugs and longevity in a geriatric population. In: Platelets, drugs and thrombosis. Symposium Hamilton 1972. Karger, Basel, pp 284–291
Danhof M, De Groot-van der Vis E, Breimer DD (1979) Assay of antipyrine and its primary metabolites in plasma, saliva and urine by HPLC, and some preliminary results in man. Pharmacology 18: 210–223
Danhof M, Verbeek RMA, Van Boxtel CJ, Beoijinga JK, Breimer DD (1982) Differential effects of enzyme induction on antipyrine metabolite formation. Br J Clin Pharmacol 13: 379–386
Dieterle W, Faigle JW, Moppert J (1980) New metabolites of sulphinpyrazone in man. Drug Res 30: 989–993
Kirstein Pedersen A, Jakobsen P (1979) Two new metabolites of sulphinpyrazone in the rabbit: a possible cause of the prolonged in vivo effect. Thromb Res 16: 871–876
O'Reilly RA (1982) Stereoselective interaction of sulphinpyrazone with racemic warfarin and its separated enantiomorphs in man. Circulation 65: 202–207
Ohnhaus EE, Park BK (1979) Measurement of urinary 6-β-hydroxycortisol excretion as an in vivo parameter in the clinical assessment of the microsomal enzyme-inducing capacity of antipyrine, phenobarbitone and rifampicin. Eur J Clin Pharmacol 15: 139–145
Park BK (1978) A direct radioimmunoassay for 6-β-hydroxycortisol in urine. J Steroid Biochem 9: 963–966
Park BK (1981) Assessment of urinary 6-β-hydroxycortisol as an in vivo index of mixed function oxygenase activity. Br J Clin Pharmacol 12: 97–102
Parke DV (1978) Toxicological consequences of enzyme induction and inhibition. In: Gorrod JW (ed) Aspects of drug toxicity. Taylor and Francis, London
Sachs L (1978) Angewandte Statistik. Springer, Berlin Heidelberg New York, pp 368–369
Sanghvi A, Wight C, Parikh B, Desai H (1973) Urinary 17-hydroxycorticosteroids determination with p-hydrazinbenzenesulfonic acid-phosphoric acid. Am J Clin Pathol 60: 684–690
Smythe HA, Ogryzlo MA, Murhy EA, Mustard JF (1965) The effect of sulphinpyrazone (Anturano) on platelet economy and blood coagulation in man. Can Med Assoc J 97: 818–821
Staiger CH, de Vries J, Walter E (1980) A rapid and sensitive method for the determination of antipyrine by gas-liquid chromatography with nitrogen detection. J Clin Chem Clin Biochem 18: 817–819
The Anturano Reinfarction Trial Research Group. Sulphinpyrazone in the prevention of sudden death after myocardial infarction. N Engl J Med 302: 250–256
Walter E, Hodock-Laibach P, Zimmermann R, Weber E (1979) Action and interaction of sulphinpyrazone in anticoagulated patients. Thromb Haemostas 42: 62
Walter E, Staiger CH, de Vries J, Weber E, Zimmermann R (1980) Induction of drug metabolizing enzymes by sulphinpyrazone. Eur J Clin Pharmacol 19: 353–358
Wilcox RG, Richardson D, Hampton JR, Mitchell JRA, Banks DC (1980) Sulphinpyrazone in acute myocardial infarction: studies on cardiac rhythm and renal function. Br Med J 281: 531–534
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Staiger, C., Schlicht, F., Walter, E. et al. Effect of single and multiple doses of sulphinpyrazone on antipyrine metabolism and urinary excretion of 6-beta-hydroxycortisol. Eur J Clin Pharmacol 25, 797–801 (1983). https://doi.org/10.1007/BF00542523
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DOI: https://doi.org/10.1007/BF00542523