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Naproxen pharmacokinetics in the elderly.

R A Upton, R L Williams, J Kelly

    British Journal of Clinical Pharmacology
    |August 1, 1984
    PubMed
    Summary
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    Elderly individuals show altered naproxen pharmacokinetics due to reduced protein binding, leading to higher unbound drug concentrations. This suggests a potential need for reduced naproxen dosage in older adults.

    Area of Science:

    • Pharmacology
    • Geriatrics
    • Drug Metabolism

    Background:

    • Naproxen pharmacokinetics can be affected by renal and hepatic function.
    • The influence of concurrent renal and hepatic function alterations on naproxen disposition in the elderly is not well understood.

    Purpose of the Study:

    • To investigate the impact of aging on naproxen pharmacokinetics, specifically focusing on plasma protein binding and intrinsic clearance.
    • To evaluate potential implications for naproxen dosing in the elderly population.

    Main Methods:

    • A single oral dose of naproxen (375 mg) was administered to healthy young and elderly male subjects.
    • Plasma concentrations, protein binding, and clearance (total and unbound) were measured at single-dose and steady-state conditions.

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    Main Results:

    • Total plasma clearance/bioavailability (CL/F) was lower in the elderly after a single dose but statistically indistinguishable at steady-state.
    • The fraction of unbound naproxen in plasma was doubled in elderly subjects.
    • Mean steady-state plasma concentrations were similar, but unbound concentrations were twice as high in the elderly.

    Conclusions:

    • Reduced plasma protein binding in the elderly significantly increases unbound naproxen concentrations, despite similar total plasma concentrations.
    • A 50% reduction in naproxen dose may be advisable for the elderly, pending further drug concentration-response studies.
    • Similar alterations in protein binding could contribute to benoxaprofen toxicity in the elderly.