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Age and cibenzoline disposition.

R K Brazzell, M M Rees, K C Khoo

    Clinical Pharmacology and Therapeutics
    |November 1, 1984
    PubMed
    Summary
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    Aging significantly alters cibenzoline pharmacokinetics, affecting drug clearance and half-life in healthy adults. This study reveals age-dependent changes in drug metabolism and elimination.

    Area of Science:

    • Pharmacology
    • Geriatric Medicine
    • Drug Metabolism

    Background:

    • Cibenzoline is an antiarrhythmic drug.
    • Understanding drug pharmacokinetics in aging populations is crucial for safe and effective dosing.

    Purpose of the Study:

    • To investigate the impact of age on the oral pharmacokinetics of cibenzoline in healthy adults.
    • To identify age-related changes in cibenzoline absorption, distribution, metabolism, and excretion.

    Main Methods:

    • Single oral dose (160 mg) of cibenzoline administered to 36 healthy subjects aged 20-80 years.
    • Blood and urine samples collected over 72 hours post-dose.
    • Plasma and urine cibenzoline concentrations measured using High-Performance Liquid Chromatography (HPLC).

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    Main Results:

    • Significant age-related linear relationships observed for maximum plasma concentration (Cmax), urinary recovery (Xu), half-life (t 1/2), oral clearance (ClT), renal clearance (ClR), non-renal clearance (ClNR), and volume of distribution (Vd).
    • Cmax, Xu, and t 1/2 increased with age, while ClT, ClR, ClNR, and Vd decreased.
    • Mean ClT decreased from 999 ml/min in the 20-30 year group to 465 ml/min in the 70-80 year group.
    • Mean t 1/2 increased from 7 hours to 10.5 hours across the age range.

    Conclusions:

    • Age significantly influences cibenzoline pharmacokinetics in healthy individuals.
    • Reduced oral clearance and prolonged half-life in older adults necessitate potential dose adjustments.
    • Age-related changes in both renal and non-renal clearance contribute to altered cibenzoline disposition.