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Related Experiment Videos

Plasma diazepam concentrations following prolonged administration

J A Gamble, J W Dundee, R C Gray

    British Journal of Anaesthesia
    |November 1, 1976
    PubMed
    Summary
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    Long-term intravenous diazepam (5-10 mg) leads to accumulation of both the drug and its N-desmethyl metabolite. The metabolite concentration increases throughout treatment, with slow elimination after discontinuation.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacy
    • Drug Metabolism

    Background:

    • Diazepam is a commonly prescribed benzodiazepine.
    • Understanding diazepam and its metabolite pharmacokinetics is crucial for safe and effective use.

    Purpose of the Study:

    • To quantify plasma concentrations of diazepam and its active metabolite, N-desmethyl diazepam.
    • To investigate the accumulation and elimination kinetics of diazepam and N-desmethyl diazepam during prolonged intravenous administration.

    Main Methods:

    • Patients received intravenous diazepam (5 mg or 10 mg) every 4 hours for 6 to 22 days.
    • Plasma concentrations of diazepam and N-desmethyl diazepam were measured throughout the study period and after discontinuation.

    Main Results:

    Related Experiment Videos

    • Both diazepam and N-desmethyl diazepam accumulated in plasma at both dosage levels.
    • N-desmethyl diazepam concentrations reached 2-3 times that of the parent drug.
    • Diazepam plasma levels plateaued around 8 days, while N-desmethyl diazepam continued to rise.
    • Following discontinuation, diazepam exhibited a half-life of 2-4 days, and N-desmethyl diazepam showed a longer half-life of 4-8 days.

    Conclusions:

    • Prolonged i.v. administration of diazepam results in significant accumulation of both the parent drug and its active metabolite.
    • The sustained increase and slow elimination of N-desmethyl diazepam suggest potential for prolonged effects and drug interactions.