Sulphinpyrazone metabolism during long‐term therapy.

Abstract

1 The plasma concentrations of sulphinpyrazone and four of its metabolites are reported together with the amounts excreted in urine. Eight insulin-requiring diabetics were investigated, all treated with sulphinpyrazone 600-800 mg day-for 2.5 years or more. 2 Blood samples were drawn before the first morning dose and 2 h later. The mean plasma concentrations were (t = 0 h -t = 2 h): sulphinpyrazone 7.1-16.0>gml-'; sulphide 2.8-4.3 gigml-1; sulphone 1.7-4.8 pgmlm'; p-OH-sulphide 0.67-0.89 Fg ml-; p-OH-sulphinpyrazone 0. 10-0.16 pg ml-'. Statistically significant correlations were found between the plasma concentrations at t = 0 of the sulphide and the p-OH-sulphide and that of sulphinpyrazone. 3 In urine, a very wide range in excretion of unconjugated compounds was observed. Sulphinpyrazone were excreted in amounts corresponding to 1-30% of the daily dose. The metabolites were generally excreted in amounts corresponding to less than 1 % of the daily dose; however, up to 3% was found as the sulphone. 4 Increases of the concentrations of all compounds in urine were found after treatment with f-glucuronidase indicating 0-conjugation with glucuronic acid. 5 Since both the sulphide and the sulphone were found more active as inhibitors of platelet function in vitro than their parent compound, they may together constitute the major part of the platelet inhibitory drug activity in plasma during long-term therapy with sulphinpyrazone.

Endogenous prostacyclin biosynthesis and platelet function during selective inhibition of thromboxane synthase in man.

“…Arachidonic acid-induced platelet aggregation is the most sensitive indicator of cyclooxygenase-dependent inhibition of platelet aggregation ex vivo. In particular, the lag time before the onset of aggregation represents a sensitive quantitative measurement of inhibition of arachidonic-induced platelet activation (27,28). Weak cyclooxygenase inhibitors, such as sulfinpyrazone and its sulfide and sulfone metabolites, consistently inhibit aggregation induced by arachidonic acid, but not by other platelet agonists, such as collagen (27).…”

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

“…I). 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).…”