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Heparin kinetics determined by three assay methods

T D Bjornsson, K M Wolfram, B B Kitchell

    Clinical Pharmacology and Therapeutics
    |January 1, 1982
    PubMed
    Summary
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    Heparin

    Area of Science:

    • Pharmacology
    • Biochemistry

    Background:

    • Heparin is a widely used anticoagulant.
    • Understanding its pharmacokinetic profile is crucial for safe and effective use.
    • Heparin's dose-response can vary, necessitating kinetic studies.

    Purpose of the Study:

    • To investigate the dose-dependent pharmacokinetics of heparin in humans.
    • To compare heparin's kinetic parameters across different assay methods.
    • To elucidate the mechanisms underlying heparin's variable kinetics.

    Main Methods:

    • Four healthy subjects received three different intravenous doses of heparin (25, 50, 75 units/kg).
    • Plasma samples were collected and assayed for heparin activity using activated partial thromboplastin time, thrombin time, and chemical neutralization.

    Related Experiment Videos

  • Pharmacokinetic parameters including half-life, total clearance (Cl), and volume of distribution (Vd) were calculated.

    • Main Results:

    • Heparin exhibited dose-dependent kinetics, with increasing biologic half-life and decreasing total clearance (Cl) at higher doses.
    • Apparent volume of distribution (Vd) remained unchanged across doses.
    • Significant differences in kinetic parameters were observed between assay methods, with chemical neutralization yielding higher Cl and Vd values.

    Conclusions:

    • Heparin's dose-dependent kinetics are primarily driven by a decrease in total clearance with increasing dose.
    • Assay methodology significantly influences measured heparin kinetic parameters.
    • In vivo activation of heparin's anticoagulant properties may explain assay-dependent kinetics.