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Related Experiment Videos

Diazepam kinetics in acute alcohol withdrawal.

S M Pond, M Phillips, N L Benowitz

    Clinical Pharmacology and Therapeutics
    |June 1, 1979
    PubMed
    Summary

    Acute alcohol withdrawal speeds up diazepam elimination, but this does not explain high drug doses. Further research is needed to understand diazepam pharmacokinetics in alcoholism.

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    Area of Science:

    • Pharmacology
    • Clinical Pharmacy
    • Neuroscience

    Background:

    • Alcohol withdrawal syndrome is a complex condition requiring pharmacologic management.
    • Diazepam is frequently used to manage alcohol withdrawal symptoms.
    • Understanding diazepam pharmacokinetics during withdrawal is crucial for optimizing treatment.

    Purpose of the Study:

    • To compare diazepam pharmacokinetics in alcoholic subjects during acute withdrawal versus after detoxification.
    • To investigate the influence of alcohol withdrawal on diazepam disposition and protein binding.

    Main Methods:

    • Within-subject design comparing diazepam kinetics in 7 alcoholic subjects.
    • Measurements taken during acute alcohol withdrawal and after detoxification.
    • Analysis of plasma diazepam concentrations, elimination half-life (t1/2 alpha and terminal), clearance, and volume of distribution.
    • Assessment of plasma protein binding.

    Main Results:

    • The initial rapid decline of plasma diazepam concentrations (t1/2 alpha) was significantly faster during withdrawal (0.21 hr) compared to after withdrawal (0.44 hr).
    • Mean terminal half-life, clearance, and volume of distribution did not significantly change between conditions.
    • Plasma protein binding of diazepam was lower in alcoholic patients (93.4%) compared to healthy controls (97.0%).

    Conclusions:

    • Acute alcohol withdrawal accelerates the initial elimination of diazepam.
    • Observed pharmacokinetic changes during withdrawal do not fully account for the high diazepam doses often needed for treatment.
    • Lower protein binding in alcoholic patients may contribute to altered diazepam disposition.

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