Biliary metabolites of the anti-inflammatory drug 2-acetamido-4-(chloromethyl)thiazole.
The mechanism for the formation of a class of sulfur-containing conjugates of xenobiotics was further investigated in this report. The major biliary metabolites of 2-acetamido-4-(chloromethyl)thiazole in the rat were found to be the mercapturic acid conjugate of 2-acetamido-4-methylthiazole and the glucuronic acid conjugate of 2-acetamido-4-(mercaptomethyl)thiazole. When these two compounds were introduced directly into the cecum of the rat, 2-acetamido-4-[(methylsulfinyl)methyl]thiazole and 2-acetamido-4-[(methylsulfonyl)methyl]thiazole were found as urinary metabolites. These results give strong support to a proposed mechanism in which intestinal microfloral metabolism of biliary metabolites, together with enterohepatic circulation, is necessary for the formation and urinary excretion of the 4-(methylthiomethyl), 4-(methylsulfinyl-methyl), and 4-(methylsulfonylmethyl) analogs of 2-acetamido-4-(chloromethyl)thiazole in the rat.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000652:urine; D001646:Bile / Q000378:metabolism*; D002432:Cecum / Q000378:metabolism; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D013844:Thiazoles; C023732:2-acetamido-4-chloromethylthiazole