RT Journal Article
SR Electronic
T1 Biliary metabolites of the anti-inflammatory drug 2-acetamido-4-(chloromethyl)thiazole.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 654
OP 656
VO 10
IS 6
A1 Rafter, J J
A1 Bakke, J E
YR 1982
UL http://dmd.aspetjournals.org/content/10/6/654.abstract
AB 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.