Abstract
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.
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|