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Quazepam kinetics in the elderly.

J M Hilbert, M Chung, E Radwanski

    Clinical Pharmacology and Therapeutics
    |October 1, 1984
    PubMed
    Summary
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    This study investigated quazepam pharmacokinetics in geriatric patients. Elderly individuals showed significantly longer elimination half-lives for N-desalkyl-2-oxoquazepam, impacting drug metabolism.

    Area of Science:

    • Pharmacology
    • Geriatric Medicine
    • Clinical Pharmacy

    Background:

    • Benzodiazepine hypnotics are commonly prescribed for sleep disorders.
    • Age-related changes in drug metabolism can affect pharmacokinetic profiles.
    • Understanding quazepam's behavior in the elderly is crucial for safe prescribing.

    Purpose of the Study:

    • To determine the pharmacokinetic profile of quazepam in geriatric subjects.
    • To compare the kinetics of quazepam and its active metabolites in the elderly versus younger populations.
    • To assess the impact of aging on the elimination of quazepam and its metabolites.

    Main Methods:

    • 10 geriatric subjects received a single 15-mg dose of quazepam.
    • Plasma concentrations of quazepam and its metabolites (2-oxoquazepam, N-desalkyl-2-oxoquazepam) were measured over 672 hours.

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  • Gas-liquid chromatography (GLC) was used for precise quantification.
  • Pharmacokinetic parameters were analyzed using a two-compartment open model.

    • Main Results:

    • Quazepam exhibited rapid absorption (t1/2 = 0.8 hr) and a mean elimination half-life (t1/2 beta) of 53.3 hr.
    • The metabolite 2-oxoquazepam showed similar rapid formation and elimination kinetics to quazepam.
    • N-desalkyl-2-oxoquazepam displayed a significantly prolonged elimination half-life (189.7 hr) in the elderly, more than double that of young subjects.

    Conclusions:

    • Quazepam and its primary metabolite 2-oxoquazepam show minimal age-related changes in elimination half-life.
    • The prolonged elimination of N-desalkyl-2-oxoquazepam in geriatric patients suggests potential for accumulation.
    • These findings highlight the importance of considering age-specific metabolic differences for benzodiazepine hypnotics like quazepam.