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Tracazolate metabolites in rat tissue.

F R Zuleski, K M Kirkland, M D Melgar

    Drug Metabolism and Disposition: the Biological Fate of Chemicals
    |March 1, 1985
    PubMed
    Summary
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    High-performance liquid chromatographic determination of tracazolate and its major metabolite in plasma.

    Journal of pharmaceutical sciences·1984

    Tracazolate undergoes extensive biotransformation in male rats, producing numerous lipophilic metabolites in plasma, brain, and fat tissue. These metabolites result from various reactions including hydrolysis, oxidation, and dealkylation.

    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Toxicology

    Background:

    • Tracazolate is a compound that undergoes biotransformation.
    • Understanding drug metabolism is crucial for assessing efficacy and safety.

    Purpose of the Study:

    • To identify and characterize the metabolites of tracazolate in male rats.
    • To investigate the distribution of tracazolate and its metabolites in various tissues.

    Main Methods:

    • Oral administration of tracazolate to male rats.
    • Analysis of plasma, brain, and fat extracts using mass spectrometry.
    • Coadministration of stable carbon-13 labeled tracazolate to aid metabolite identification.
    • High-performance liquid chromatography (HPLC) for isolation of specific metabolites.

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    Main Results:

    • Twenty-one metabolites were identified in plasma.
    • Metabolites were formed through hydrolysis, oxidation, dealkylation, and ethyl group conversion.
    • Tracazolate and 12 metabolites were found in brain tissue.
    • Tracazolate and 9 metabolites were detected in fat tissue.
    • A novel, less polar metabolite, 1-vinyl tracazolate, was identified.

    Conclusions:

    • Tracazolate undergoes extensive biotransformation into diverse lipophilic metabolites.
    • Metabolites are distributed in plasma, brain, and fat tissues.
    • The identified metabolic pathways provide insights into tracazolate's pharmacokinetic profile.