Pharmacokinetics of single doses of sulphinpyrazone and its major metabolites in plasma and urine.
1 High pressure liquid chromatographic assays for the estimation of sulphinpyrazone and its sulphide, sulphone and p-hydroxy metabolites in plasma and urine are described. 2 Five normal volunteers received 200 mg and 400 mg sulphinpyrazone orally. Sulphinpyrazone was rapidly absorbed and eliminated with a half-life of approximately 4 h irrespective of dose. Peak plasma concentrations and area under the plasma concentration-time curves (AUC) were consistent with linear pharmacokinetic behaviour. 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-1 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.
D000328:Adult; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D013440:Sulfides / Q000378:metabolism; D013442:Sulfinpyrazone / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013450:Sulfones / Q000378:metabolism
D001798:Blood Proteins; D013440:Sulfides; D013450:Sulfones; D013442:Sulfinpyrazone