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Clinical Pharmacokinetics and Potentially Important Drug Interactions of Sulphinpyrazone

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Summary

Sulphinpyrazone is a derivative of Phenylbutazone. It was originally introduced as a uricosuric agent but in recent years it has been investigated for effects on platelet function.

Sulphinpyrazone and its metabolites can be measured in blood and urine using high performance liquid chromatography and gas chromatography-mass spectrometry. It is almost completely absorbed and maximum plasma concentrations are found about 2 hours after oral administration. The decay of the plasma concentration of sulphinpyrazone when administered intravenously is best described by an open 3-compartment model with half-lives of the α-, β-and γ-phases at about 0.3, 3 and 6 hours, respectively. The volume of distribution has been calculated to be 60ml/kg. Sulphinpyrazone and its unconjugated metabolites are strongly (98 to 99%) bound to plasma proteins. The total clearance of sulphinpyrazone has been estimated at 20 to 25ml/min.

25 to 50% of a sulphinpyrazone dose is excreted in the urine in unchanged form. The remainder is metabolised via several pathways; a sulphide metabolite is the predominant circulating metabolite reaching levels about 25 % of that of sulphinpyrazone. The sulphide is probably important for the antiplatelet effect of sulphinpyrazone, but not for the uricosuric action. The sulphone metabolite and parahydroxylated metabolites are of minor quantitative significance. All metabolites are excreted as C-glucuronides;onlya small proportion of metabolites is excreted in O-glucuronidated or in unconjugated form in urine.

Decreased renal function apparently does not influence plasma concentrations of sulphinpyrazone, and dosage changes in patients with renal dysfunction do not seem warranted.

Several drug interactions have been reported involving displacement from plasma proteins, inhibition and induction of hepatic microsomal metabolism, and influence on renal tubular secretion. Clinically the most important interactions seem to be potentiation of the effects of oral anticoagulants, Phenytoin and tolbutamide, and inhibition of the uricosuric effect of probenecid and salicylate.

No data comparing plasma concentrations and clinical effects are available.

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Authors and Affiliations

  1. Department of Pharmacology, University of Aarhus, Denmark

    A. Kirstein Pedersen, P. Jakobsen, J. P. Kampmann &  J. Mølholm Hansen

  2. Medical Department P, Bispebjerg Hospital, Denmark

    A. Kirstein Pedersen, P. Jakobsen, J. P. Kampmann &  J. Mølholm Hansen

  3. Department of Internal Medicine and Endocrinology F, Herlev University Hospital, Copenhagen, Denmark

    A. Kirstein Pedersen, P. Jakobsen, J. P. Kampmann &  J. Mølholm Hansen

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  2. P. Jakobsen
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Pedersen, A.K., Jakobsen, P., Kampmann, J.P. et al. Clinical Pharmacokinetics and Potentially Important Drug Interactions of Sulphinpyrazone. Clin Pharmacokinet 7, 42–56 (1982). https://doi.org/10.2165/00003088-198207010-00003

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