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Amiodarone pharmacokinetics.

D W Holt, G T Tucker, P R Jackson

    American Heart Journal
    |October 1, 1983
    PubMed
    Summary
    This summary is machine-generated.

    Amiodarone exhibits extensive distribution, low clearance, and a prolonged elimination half-life, averaging around 40 days in patients. Fat tissue acts as a significant reservoir for amiodarone and its metabolite.

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    Area of Science:

    • Pharmacology
    • Clinical Pharmacy
    • Drug Metabolism

    Background:

    • Amiodarone is a widely used antiarrhythmic drug.
    • Understanding its pharmacokinetic profile is crucial for effective therapeutic management.
    • Previous studies have indicated a complex disposition of amiodarone.

    Purpose of the Study:

    • To characterize the single-dose pharmacokinetics of amiodarone.
    • To determine key pharmacokinetic parameters including volume of distribution, clearance, and elimination half-life.
    • To investigate the elimination profile and tissue distribution of amiodarone and its primary metabolite, desethylamiodarone.

    Main Methods:

    • Volunteer subjects received a single 400 mg dose of amiodarone.
    • Administration was conducted via both intravenous and oral routes.

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  • Pharmacokinetic parameters were analyzed from plasma and tissue samples.

    • Main Results:

    • Amiodarone demonstrated a very large volume of distribution and low total clearance.
    • The terminal elimination half-life was long and variable, approximately 40 days in patients.
    • Desethylamiodarone exhibited a longer terminal elimination half-life than amiodarone.
    • High drug concentrations were found in tissues, with adipose tissue serving as a substantial reservoir.

    Conclusions:

    • Amiodarone possesses unique pharmacokinetic properties characterized by extensive tissue distribution and prolonged elimination.
    • The long half-life and tissue accumulation, particularly in fat, contribute to its sustained effects and potential for delayed toxicity.
    • The pharmacokinetic profile necessitates careful consideration in dosing and monitoring, especially after drug withdrawal.