Sulphinpyrazone metabolism during long-term therapy.

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-1 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 microgram ml-1; sulphone 1.7-4.8 microgram ml-1; p-OH-sulphide 0.67-0.89 microgram ml-1; p-OH-sulphinpyrazone 0.10-0.16 microgram ml-1. 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 to amounts corresponding to less than 1% of the daily dose; however, up to 3% was found as the sulphone. 4 Increases of the concentration of all compounds in urine were found after treatment with beta-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.