TY - JOUR T1 - Biliary metabolites of the anti-inflammatory drug 2-acetamido-4-(chloromethyl)thiazole. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 654 LP - 656 VL - 10 IS - 6 AU - J J Rafter AU - J E Bakke Y1 - 1982/11/01 UR - http://dmd.aspetjournals.org/content/10/6/654.abstract N2 - 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. ER -