Role of the gut flora in the reduction of sulfinpyrazone in humans.

Peak plasma concentrations of sulfinpyrazone occurred about 2 h after administration of a single oral dose (200 mg tablet) to 11 normal volunteers. In contrast, the peak concentrations of the active sulfide metabolite occurred 15 h after dosing. Concurrent oral administration of metoclopramide with sulfinpyrazone resulted in a 4-fold decrease in the time to peak sulfide concentrations and a 3-fold increase in the amounts formed. A slow release formulation showed a low, variable bioavailability, but the proportion of sulfide was 3-fold higher based on the ratio of the area under the plasma concentration-time curve of the sulfide to that of the parent compound. Intravenous administration of sulfinpyrazone demonstrated that the tablets had a high bioavailability (about 90%), and the time to peak plasma concentration of the sulfide and the amount formed were similar to those seen after oral administration. Patients who had undergone surgical removal of the distal part of the intestine had normal plasma concentrations of sulfinpyrazone, but negligible amounts of the sulfide, after oral administration of sulfinpyrazone. The ileostomy effluent of such patients showed little ability to reduce sulfinpyrazone in vitro, in contrast to the extensive reduction detected with normal feces. These data demonstrate that the hind gut microflora are the principal and possibly the only site of reduction of sulfinpyrazone to its active sulfide metabolite in humans.