A metabolite of sulphinpyrazone that is largely responsible for the effect of the drug on the platelet prostaglandin pathway

Pay, Graham F.; Wallis, Robert B.; Zelaschi, Daniela

doi:10.1042/bst0080727

Cited by 8 publications

(3 citation statements)

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“…Table 3 details some pharmacokinetic parameters derived from the plasma concentrations of the sulphide and sulphone metabolite of sulphinpyrazone. As found by Dieterle et al (1980) the levels of sulphone were low and peaked earlier than the sulphide at about 2-3 h. The peak plasma concentrations of sulphide developed at about 13-16 h. The AUCs of the sulphide (a metabolite with putative therapeutic action on platelets-Kirstein Pedersen & Jacobsen, 1979;Pay et al, 1980) show marked interindividual variation. The ratios of AUCs after 200 and 400 mg would suggest a disproportionate formation of sulphide in some individuals.…”

Section: Resultsmentioning

confidence: 79%

Pharmacokinetics of single doses of sulphinpyrazone and its major metabolites in plasma and urine.

Bradbrook¹,

John²,

Morrison³

et al. 1982

Brit J Clinical Pharma

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3 Plasma concentrations of the sulphone were low and peaked before those of the sulphide; its mean half-life was 3.1 h. The sulphide, which may be the sulphinpyrazone metabolite with activity on platelets, was eliminated with a mean half-life of 13.4 h. The AUC increases with dose of both metabolites suggested non-linearity. 4 Approximately 45-50% of the administered dose was eliminated in the urine as unchanged drug or as sulphone or p-hydroxy-sulphinpyrazone. The sulphide metabolite was not detected in the urine. The renal clearance of sulphinpyrazone was approximately 18 ml min-and that for the sulphone was similar. Sigma minus plots of the urinary excretion yielded half-lives of 3.5 h for the sulphone and 1 h for p-hydroxy-sulphinpyrazone.

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Section: Resultsmentioning

confidence: 79%

Pharmacokinetics of single doses of sulphinpyrazone and its major metabolites in plasma and urine.

Bradbrook¹,

John²,

Morrison³

et al. 1982

Brit J Clinical Pharma

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“…Its plasma concentrations during long term dosing are between 25 and 100% of those of the parent compound (Kirstein Pedersen & Fitzgerald 1985;Kirstein Pedersen & Jakobsen 1981;Rosenkranz et al 1983). Since this metabolite has been reported to be up to 16 times more potent as an inhibitor of platelet cyclo-oxygenase than sulphinpyrazone it- self, the metabolite may be responsible for the main action on platelets during regular dosing (Del Maschio et al 1984;Pay et al 1980). Studies in animals (Renwick et al 1982;Strong et al 1984b) and in humans (Strong et al 1984a) have shown that the gut flora are responsible for the production of the active sulphide metabolite.…”

Section: Clinical Pharmacology Group University Of Southampton Soutmentioning

confidence: 99%

Effects of Ischaemic Heart Disease, Crohnʼs Disease and Antimicrobial Therapy on the Pharmacokinetics of Sulphinpyrazone

Strong

Angus

Oates

et al. 1986

Clinical Pharmacokinetics

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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 (200 mg 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.

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“…In this active form, less than 12% is absorbed from the gut. The inactive monoethyl ester derivative enalapril has an improved absorption of between 50% and 75% (Swanson et al, 1984;Ulm et al, 1982) and conversion to enalaprilat occurs by deesterification in the liver (Howlett, 1983 (Buchanan et al, 1978;Pay et al, 1980). SulPlasmin phinpyrazone may therefore be considered a prodrug for its antiplatelet effects.…”

Section: Cardiovasclular Systemnmentioning

confidence: 99%

Prodrugs.

and

George

1989

Brit J Clinical Pharma

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A metabolite of sulphinpyrazone that is largely responsible for the effect of the drug on the platelet prostaglandin pathway

Cited by 8 publications

References 0 publications

Pharmacokinetics of single doses of sulphinpyrazone and its major metabolites in plasma and urine.

Pharmacokinetics of single doses of sulphinpyrazone and its major metabolites in plasma and urine.

Effects of Ischaemic Heart Disease, Crohnʼs Disease and Antimicrobial Therapy on the Pharmacokinetics of Sulphinpyrazone

Prodrugs.

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