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Sulfinpyrazone: A Review of its Pharmacological Properties and Therapeutic Use

Drugs volume 20, pages 179–197 (1980)Cite this article

Summary

Synopsis: Sulfinpyrazone1 has long been recognised as a potent uricosuric agent, but has more recently been studied extensively as a platelet inhibitor and antithrombotic agent. It is active in man following oral administration and has been reported to be effective in reducing the incidence of transient ischaemic attacks, thromboembolism associated with vascular and cardiac prostheses, recurrent venous thrombosis, arteriovenous shunt thrombosis and sudden cardiac death following myocardial infarction. Sulfinpyrazone has not been demonstrated to be effective in preventing or reducing the risk of stroke or death in patients with cerebrovascular disease with a recent history of cerebral or retinal ischaemic attacks.

The normal total dose of sulfinpyrazone as an antithrombotic agent is 800mg daily. The drug has been used continuously for up to 4 years with no serious adverse reactions or laboratory abnormalities. There has been no apparent diminution of effect with time. Sulfinpyrazone is not a substitute for conventional anticoagulant agents (e.g. the coumarin derivatives) in the treatment of venous thrombosis, but is an important drug for the treatment of conditions associated with arterial thrombosis and possibly for the prophylaxis of recurrent venous thrombosis.

Pharmacodynamic Studies: In animals and man, sulfinpyrazone extends platelet survival and correspondingly reduces platelet turnover. The drug also reduces mural thrombus formation and platelet aggregation which have been induced by various stimuli in numerous animal models. Platelet aggregates which form as a result of complement-dependent immunological responses are also inhibited by sulfinpyrazone with the result that graft function (e.g. kidney transplantation in the dog) is prolonged. With relatively low oral doses, sulfinpyrazone stimulates fibrinolytic activity as evidenced by the normalisation of prolonged euglobulin clot lysis time in rats with kaolin paw edema. In baboons pretreated with infusions of homocysteine to induce endothelial damage, sulfinpyrazone significantly normalised platelet turnover and aortic endothelial desquamation. Significant antiarrhythmic effects have been observed with sulfinpyrazone in several animal models including cats, dogs and rats.

Pharmacokinetic Studies: Sulfinpyrazone is rapidly absorbed from the gastrointestinal tract and is more than 95% protein-bound. In 1 study in normal volunteers, the half-life was calculated to be from 2.2 to 2.7 hours. However, a prolonged platelet inhibitory effect with sulfinpyrazone has been reported following a single oral dose in human volunteers (up to 72 hours depending on the method used). Approximately 50% of the drug is excreted unchanged in the urine after a single dose.

Therapeutic Trials: In an extensive double-blind investigation in 1558 recent myocardial infarction patients, sulfinpyrazone significantly reduced cardiac deaths over a 2-year observation period as compared to placebo. This protective effect was particularly marked in the prevention of sudden cardiac death during the second through seventh month immediately following a myocardial infarction. A similar decrease in deaths of vascular origin was recorded in a 4-year study of geriatric patients with atherosclerosis.

In patients with transient cerebral ischaemia, sulfinpyrazone has been reported to increase platelet survival time and significantly reduce the frequency of ischaemic episodes. In another study, the drug significantly reduced episodes of amaurosis fugax. Nevertheless, in a large multicentre study, sulfinpyrazone did not reduce the risk of continuing transient ischaemic attacks, stroke or death in patients with transient cerebral or retinal ischaemia.

Arteriovenous shunt thrombosis and thrombus formation in arteriovenous fistulas and bovine grafts are highly susceptible to the antithrombotic effect of sulfinpyrazone. Chronic haemodialysis patients and patients with end-stage renal disease tolerated the drug well for up to 12 months of observation.

Sulfinpyrazone has been very effective in the prophylaxis of recurrent venous thrombosis. In 1 double-blind study the drug significantly reduced the incidence of venous thrombi over 24 months of observation as compared to placebo.

Side Effects: Sulfinpyrazone is well tolerated with chronic use, even in geriatric patients and patients with severe renal disease. The most common side effects are mild upper gastrointestinal disturbances. Blood dyscrasias and allergic reactions have been observed only occasionally, without establishment of a cause-effect relationship.

Dosage: The usual recommended adult dose is 800mg per day given in 4 doses. The total daily dose should not exceed 1000mg per day. Sulfinpyrazone should be taken with meals or milk.

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  1. Pharmaceuticals Division, C/o Dr Marc D. Cohen, Ciba-Geigy Corporation, Summit, New Jersey, 07901, USA

    E. H. Margulies

  2. Pharmaceuticals Division, Ciba-Geigy Corporation, Horsham, West Sussex, England

    A. M. White

  3. Temple University School of Medicine, 3400 N. Broad St., Philadelphia, Pennsylvania, 19140, USA

    S. Sherry

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‘Anturane’ (Ciba-Geigy).

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Margulies, E.H., White, A.M. & Sherry, S. Sulfinpyrazone: A Review of its Pharmacological Properties and Therapeutic Use. Drugs 20, 179–197 (1980). https://doi.org/10.2165/00003495-198020030-00002

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  • DOI: https://doi.org/10.2165/00003495-198020030-00002

Keywords

  • Newcastle Disease Virus
  • Sulfinpyrazone
  • Hamster Cheek Pouch
  • Amaurosis Fugax
  • Sulfin