1. Transformation of dithiopyr by rat liver enzymes in vitro produced the corresponding monoacids as the predominant metabolites. 2. Transformations of the methylthioester functional groups in dithiopyr to the monoacids were mediated via rat liver microsomal oxygenases, and not via esterases. 3. Based on the formation of a dithiopyr-glutathione conjugate, the mechanism of monoacid formation is believed to proceed through an initial sulphur oxidation of the methylthioester group and a subsequent nucleophilic displacement reaction.
1. Thiazopyr was metabolized by liver microsomes from male Sprague-Dawley rats to a previously unidentified metabolite. 2. The new metabolite was identified by coelution with an authentic standard in hplc and by electrospray lc/ms as the corresponding carboxylic acid. 3. Formation of the carboxylic acid metabolite was inhibited in the presence of mono-oxygenase inhibitors including piperonyl butoxide, 1-aminobenzotriazole, metyrapone and tetcyclacis. 4. Transformation of thiazopyr to its carboxylic acid by rat liver microsomes is mediated by mono-oxygenases and not hydrolases.
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