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Related Experiment Videos

Physiologic disposition of lergotrile.

A Rubin, L Lemberger, P Dhahir

    Clinical Pharmacology and Therapeutics
    |March 1, 1978
    PubMed
    Summary

    Lergotrile, an ergot alkaloid, is rapidly absorbed and extensively metabolized in humans. Its metabolites are primarily eliminated via feces and urine, with some N-demethylation occurring.

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    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Human Physiology

    Background:

    • Lergotrile, an ergot alkaloid, is recognized for treating hyperprolactinemia and Parkinson's disease due to its dopaminergic activity.
    • Understanding its physiological disposition is crucial for optimizing therapeutic use.

    Purpose of the Study:

    • To investigate the pharmacokinetic profile and metabolic fate of lergotrile in human volunteers.
    • To identify major metabolites and excretion pathways of lergotrile.

    Main Methods:

    • Administration of radiolabeled N-14CH3-lergotrile to human volunteers.
    • Analysis of plasma, urine, feces, and expired breath for radioactivity and metabolites.
    • Identification of specific metabolites using chemical characterization.

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    Main Results:

    • Lergotrile is rapidly absorbed from the gastrointestinal tract.
    • The majority of radioactivity in plasma consists of lergotrile metabolites.
    • Excretion occurs mainly in feces (approx. 60%) and urine (approx. 20%), with 7% as 14CO2 in breath.
    • Key metabolites identified include 13-OH-lergotrile in feces and a carboxyl derivative in urine.
    • N-demethylation to norlergotrile was confirmed by 14CO2 in expired air.

    Conclusions:

    • Lergotrile undergoes significant metabolism in humans, with diverse metabolic pathways including hydroxylation, C8-acetonitrile conversion, and N-demethylation.
    • The primary routes of elimination for lergotrile and its metabolites are fecal and urinary excretion.
    • These findings provide essential data for understanding lergotrile's pharmacokinetics and informing clinical applications.