Printed in U.S.A. The Formation of 1-Thiocarbamoyl-2-Imidazolidinone from Niridazole in Mouse Intestine1

Tracy, James W. and Leslie T. Webster, Jr.: The formation of treatment of mice with neomycin sulfate reduced the amount 1-thiocarbamoyl-2-imidazo!idinone from niridazole in mouse of TCI excreted in the urine by about 90 % over a 24-hr period, intestine. J. Pharmacol. Exp. Ther. 21 7: 363-368, 1 981. but did not affect the amount of 4-hydroxyniridazole excreted. Injection of niridazole into isolated segments of mouse intestine This study was designed to identify the site of formation of 1- resulted in TCI production, with the greatest conversion noted thiocarbamoyl-2-imidazolidinone (TCI), a potent immunoactive in the Caecum. Subsequent incubation of niridazole with sus-metabolite of the antihelminthic drug, niridazole. When nirida- pensions of mouse caecum contents in vitro also resulted in zole was administered intragastrically to C57B1/6J mice, a 4- the formation of TCI, but not 4-hydroxyniridazole. Attempts to hr delay was observed before TCI was detected in the serum. demonstrate TCI formation in vitro with various fractions of By contrast, 4-hydroxyniridazole, a marker of hepatic nirida- mouse liver were unsuccessful. These results indicate a dis-zole metabolism, appeared in the serum within 30 mm. Chang- soCiation of TCI formation from the major hepatic pathway of ing the route of niridazole administration from intragastric to niridazole metabolism and support the view that TCI is formed intracaecal abolished the lag period in the rise of serum TCI from niridazole in the gastrointestinal tract as a result of the concentrations relative to the 4-hydroxyniridazole marker. Pre- action of intestinal microflora