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Amrinone metabolism

M P Kullberg, G B Freeman, C Biddlecome

    Clinical Pharmacology and Therapeutics
    |March 1, 1981
    PubMed
    Summary
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    This study developed methods to measure amrinone and its metabolite in humans. Amrinone is eliminated from the blood with a half-life of approximately 2.6 hours, with most excreted unchanged in urine.

    Area of Science:

    • Pharmacokinetics
    • Analytical Chemistry

    Background:

    • Amrinone is a medication used for heart conditions.
    • Understanding amrinone's metabolism and excretion is crucial for safe and effective dosing.

    Purpose of the Study:

    • To develop and validate high-performance liquid chromatographic (HPLC) methods for quantifying amrinone and its N-acetyl metabolite.
    • To analyze amrinone pharmacokinetics in healthy men following intravenous and oral administration.

    Main Methods:

    • Development of HPLC methods for amrinone and N-acetyl amrinone analysis in plasma and urine.
    • Administration of intravenous (0.8–2.2 mg/kg) and oral (0.31–3.5 mg/kg) amrinone doses to healthy male subjects.
    • Pharmacokinetic analysis including determination of elimination half-life and urinary excretion.

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    Main Results:

    • Amrinone elimination from plasma followed first-order kinetics with a mean half-life of 2.6 ± 1.4 hours.
    • Urinary excretion of unchanged amrinone ranged from 10% to 40% of the dose within 24 hours.
    • The N-acetyl metabolite was found in minimal amounts (<2% of dose) in urine and rarely in plasma.

    Conclusions:

    • The developed HPLC methods are suitable for amrinone and metabolite analysis.
    • Amrinone is primarily eliminated unchanged in urine, with limited N-acetylation.
    • Elimination half-life appears relatively consistent, though potential dose-dependency was noted with oral administration.