Metabolic Fate and Mechanism of Action of Chloroethylthiamine

Abstract

The chick urinary metabolites of chloroethylthiamine, a potent coccidiostat , were studied. After 20mg of 35S-chloroethylthiamine was administered to chicks, 17 radioactive metabolites were separated by Amberlite CG-50 column chromatogra phy followed by cellulose thin layer chromatography.Five major metabolites were identified to be unchanged chloroethylthiamine, thiamine, thiamine anhydride , thiamine anhydride sulfoxide and thiamine anhydride sulfone. The amounts were 34.2, 3.3, 18.3, 4.9 and 4.1% of the total urinary radioactivity, respectively . After intraperitoneal administration of 35S-chloroethylthiamine, however, the forma tion of thiamine was negligible.These results suggest that the gastrointestinal tissue or the intestinal flora might play an important role in the biotransformation of chloroethylthiamine to thiamine. It was indicated that the stimulative effect of chloroethylthiamine on chick growth is due to the formation of thiamine .In the previous papers, it has been reported that chloroethylthiamine has a strong anti-thia mine activity in the intestinal absorption of thiamine of physiological levels, less than 10-6M

Metabolic Fate and Mechanism of Action of Chloroethylthiamine

“…In the previous papers (3,4), it was shown that chloroethylthiamine, not its metabolites, is the active form against the coccidium and that chloroethylthiamine markedly inhibits the active transport of thiamine from the chick small intestine, suggesting that the anticoccidial action of chloroethylthiamine is due to its property to inhibit thiamine transport.…”