New metabolites of sulfinpyrazone in man.
The disposition and metabolism of sulfinpyrazone have been studied after oral administration of 100 mg 14C-labelled drug to two male volunteers. The results confirmed earlier observations on the kinetics and biotransformation of the drug in man. Additionally, four new metabolites were identified and quantified, i.e., the sulfide analogue G 25 671 of sulfinpyrazone (Anturano), the p-hydroxy-sulfide G 33 378, the p-hydroxy-sulfone CGP 17 385 and the C(4)-glucuronide of the sulfide. In plasma, the area under the concentration-time curve (0--24 h) of sulfinpyrazone was, on an average, 61.7% of that of total 14C-substances. The AUC-value for the sulfide and the sulfone corresponded to 13.4 and 6.0%, respectively. The other, specifically measured plasma metabolites (p-hydroxy-sulfin-pyrazone, p-hydroxy-sulfide, p-hydroxy-sulfone and 4-hydroxy-sulfinpyrazone) accounted for only 1.6% or less of total AUC. Almost no sulfide was excreted in the urine. The compound was transformed to its C(4)-glucuronide, a reaction common to drugs of the dioxo-pyrazolidine series. The appearance of the sulfide in plasma may be clinically important, since this metabolite shows a strong inhibitory effect on platelet aggregation in various in vitro experimental systems.
D000328:Adult; D001711:Biotransformation; D002250:Carbon Radioisotopes; D005243:Feces / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D013442:Sulfinpyrazone / Q000097:blood / Q000378:metabolism* / Q000652:urine
D002250:Carbon Radioisotopes; D013442:Sulfinpyrazone