Metabolism of thymoxamine III. Structure elucidation of the metabolites and interspecies comparison

Abstract
The structures of six metabolites were elucidated using rat urine after intragastric administration of14C-thymoxamine by means of enzyme incubations, mass spectrometry and synthesis of metabolites: desacetylthymoxamine, N-demethyl-desacetylthymoxamine, the corresponding sulfates and glucuronides. The nature of the conjugates was confirmed by biosynthesis, i.e., co-administration of unlabeled thymoxamine and35S-sulfate or14C-glucose. The system high performance liquid chromatography-radioactivity detection was used for interspecies comparison. All biotransformation pathways are seen in rat and man. In dog and cat demethylation is a very minor reaction. Glucuronidation is not observed in the cat.

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