Summary
The effect of sulphinpyrazone administration on the anticoagulant response was investigated in five patients receiving long-term treatment with warfarin. Sulphinpyrazone caused a rapid increase in prothrombin (PT) ratio in all five patients and warfarin dose had to be reduced by a mean of 46% to maintain the PT ratio in the therapeutic range. PT ratio and daily warfarin requirement returned to previous levels when sulphinpyrazone was ceased. Warfarin protein binding was not altered during sulphinpyrazone administration and sulphinpyrazone added to plasma in vitro did not increase warfarin free fraction. The average racemic plasma warfarin concentration over a dosage interval when adjusted for warfarin dose was not altered by sulphinpyrazone administration. The most likely mechanism for this drug interaction is a stereoselective effect of sulphinpyrazone on the metabolism of the warfarin enantiomers.
Similar content being viewed by others
References
Ali M, McDonald JWD (1977) Effects of sulphinpyrazone on platelet prostaglandin synthesis and platelet release of serotonin. J Lab Clin Med 89: 868–875
Kaegi A, Pineo GF, Shimizu A, Trivedi H, Hirsh J, Gent M (1975) The role of sulphinpyrazone in the prevention of arteriovenous shunt thrombosis. Circulation 52: 497–499
Steele P, Rainwater J, Vogel R, Genton E (1978) Platelet suppressant therapy in patients with coronary artery disease. J Am Med Assoc 240: 228–231
Steele P, Rainwater J (1980) Favourable effect of sulphinpyrazone on thromboembolism in patients with rheumatic heart disease. Circulation 62: 462–465
Altman R, Boullon F, Rouvier J, Raca R, de la Fuente L, Favaloro R (1976) Aspirin and prophylaxis of thromboembolic complications in patients with substitute heart valves. J Thorac Cardiovasc Surg 72: 127–129
Dale J, Myhre E, Storstein O, Stormorken H, Efskind L (1977) Prevention of arterial thromboembolism with acetylsalicylic acid. Heart 94: 101–111
Sullivan JM, Harken JE, Gorlin R (1971) Pharmacologic control of thromboembolic complications of cardiac-valve replacement. N Engl J Med 284: 289–295
Bailey RR, Reddy J (1980) Potentiation of warfarin action by sulphinpyrazone. Lancet 1: 254
Davis JW, Johns LE (1978) Possible interaction of sulphinpyrazone with coumarins. N Engl J Med 299: 955
Mattingley D, Bradley M, Selley PJ (1978) Hazards of sulphinpyrazone. Br Med J 2: 1786–1787
Thompson PL, Serjeant C (1981) Potentially serious interaction of warfarin with sulphinpyrazone. Med J Aust 1: 41
Weiss M (1979) Potentiation of coumarin effect by sulphinpyrazone. Lancet 1: 609
Gallus A, Birkett DJ (1980) Sulphinpyrazone and warfarin: a probable drug interaction. Lancet 1: 535–536
Bjornsson TD, Blaschke TF, Meffin PJ (1977) High pressure liquid chromatographic analysis of drugs in biological fluids: Part I. Warfarin. J Pharm Sci 66: 142–144
Wong LT, Solomonraj G, Thomas BH (1978) Simple and rapid microdetermination of sulphinpyrazone in biological fluids by reversed-phase high performance chromatography. J Chromatogr 150: 521–526
Duncombe WG (1964) The colorimetric microdetermination of non-esterified fatty acids in plasma. Clin Chim Acta 9: 122–125
Birkett DJ, Meffin PJ, Wing LMH (1979) Fundamentals of Clinical Pharmacology 6. Plasma Protein Binding. Curr Ther 20: 89–99
Sellers EM (1979) The clinical importance of interactions based on displacement of protein bound drugs, in Tillement JP, editor: Advances in pharmacology and therapeutics, vol. 7 from: Biochemical clinical pharmacology. Pergamon Press, New York, pp 153–162
Lewis RJ, Trager WF, Chan KF, Breckenridge A, Orme M, Roland M, Schary W (1974) Warfarin: Stereochemical aspects of its metabolism and the interaction with phenylbutazone. J Clin Invest 53: 1607–1617
O'Reilly RA, Trager WF, Motley CH, Howald W (1980) Stereoselective interaction of phenylbutazone with [12C/13C] warfarin pseudoracemates in man. J Clin Invest 65: 746–753
O'Reilly RA (1976) The stereoselective interaction of warfarin and metronidazole in man. N Engl J Med 295: 354–357
O'Reilly RA (1980) Stereoselective interaction of trimethoprim-sulfamethoxazole with the separated enantiomorphs of racemic warfarin in man. N Engl J Med 302: 33–35
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miners, J.O., Foenander, T., Wanwimolruk, S. et al. Interaction of sulphinpyrazone with warfarin. Eur J Clin Pharmacol 22, 327–331 (1982). https://doi.org/10.1007/BF00548401
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00548401