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Related Experiment Videos

Doxepin kinetics.

V E Ziegler, J T Biggs, L T Wylie

    Clinical Pharmacology and Therapeutics
    |May 1, 1978
    PubMed
    Summary
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    Doxepin hydrochloride pharmacokinetics show a mean half-life of 16.8 hours, with significant first-pass metabolism and substantial desmethyldoxepin metabolite formation. This metabolite

    Area of Science:

    • Pharmacology
    • Clinical Pharmacokinetics

    Background:

    • Doxepin (DOX) is a tricyclic antidepressant with a complex pharmacokinetic profile.
    • Understanding its metabolism and elimination is crucial for therapeutic efficacy and safety.

    Purpose of the Study:

    • To investigate the pharmacokinetic properties of doxepin hydrochloride following oral administration.
    • To characterize the absorption, distribution, metabolism, and elimination (ADME) of DOX and its primary metabolite, desmethyldoxepin (DMD).

    Main Methods:

    • Oral administration of 75 mg doxepin hydrochloride to 7 healthy volunteers.
    • Plasma concentration measurements of DOX and DMD over time.
    • Kinetic analysis to determine half-life, volume of distribution, and first-pass metabolism.

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    Main Results:

    • Peak plasma concentrations of DOX reached within 4 hours, with a mean half-life of 16.8 hours.
    • Significant first-pass metabolism of DOX (55-87%) and substantial formation of DMD.
    • DMD exhibited a longer mean half-life (51.3 hours) compared to DOX, with no correlation between their half-lives.

    Conclusions:

    • Doxepin exhibits biphasic elimination following oral administration.
    • The extensive first-pass metabolism and prolonged half-life of desmethyldoxepin are key pharmacokinetic features.
    • DMD formation correlates with DOX plasma levels, potentially explaining observed steady-state concentrations in patients.