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Clobazam kinetics in the elderly.

D J Greenblatt, M Divoll, S K Puri

    British Journal of Clinical Pharmacology
    |November 1, 1981
    PubMed
    Summary
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    Age and sex significantly impact clobazam (CBZ) drug disposition. Elderly males showed longer elimination half-lives and reduced clearance, while women experienced less pronounced age-related changes in CBZ metabolism.

    Area of Science:

    • Pharmacology
    • Geriatric Medicine
    • Clinical Pharmacy

    Background:

    • Clobazam (CBZ) is a 1,5-benzodiazepine derivative with therapeutic applications.
    • Understanding the influence of demographic factors on drug pharmacokinetics is crucial for optimizing dosing regimens.

    Purpose of the Study:

    • To investigate the effects of age and sex on the absorption, distribution, and elimination of clobazam in healthy volunteers.

    Main Methods:

    • Single oral doses of 20 mg clobazam were administered to 29 healthy volunteers (aged 18-72 years).
    • Plasma concentrations were measured over 7 days to determine pharmacokinetic parameters.
    • Statistical analyses were performed to assess the impact of age and sex on these parameters.

    Main Results:

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    • Clobazam absorption was rapid and unaffected by age or sex.
    • Elimination half-life significantly increased with age, particularly in elderly males compared to young males.
    • Volume of distribution increased with age and was larger in women than men. Total clearance declined with age in men but not in women.
    • Age-related decline in plasma albumin concentration correlated with an increased free fraction of CBZ.

    Conclusions:

    • Age and sex are significant determinants of clobazam pharmacokinetics, influencing its elimination and distribution.
    • Metabolic pathways, such as N-demethylation, show an age-related decline in capacity, especially in men.
    • These findings highlight the need for individualized dosing strategies for clobazam based on age and sex.