Studies on metabolism of tripamide. III. Metabolic fate of 14C-tripamide in rats and rabbits.

The metabolic fate of a new antihypertensive agent, tripamide (N-(4-aza-endo-tricyclo[5.2.1.0(2,6))]-decan-4-yl)-4-chloro-3-sulfamoylbenzamide), in rats and rabbits was studied using its 14C-labeled compound. The blood level of radioactivity in both species reached the maximum at 1 hr after oral administration, indicating the rapid absorption of the drug from the gastrointestinal tract. Following either oral or intravenous administration, a high concentration was observed in the liver of rats, but it was found in the kidney of rabbits. The major metabolite was 4-chloro-3-sulfamoylbenzoic acid in tissues, urine and feces; and in both species, the unchanged drug was only detected in the kidney. The pathway of excretion of radioactivity was via urine and feces in case of rats; but in rabbits, it was predominantly excreted via urine, although significant quantities of radioactivity were excreted with feces. The radioactivity excreted in feces was attributable to that which was excreted in bile, indicating the absorption of almost all the tripamide administered in both species. During the period of repeated dosing, though blood levels increased gradually and became about 1.5 times as high as that in the single dosing, radioactivity did not accumulate in most tissues and organs.