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Steady-state distribution volume in physiologic multi-organ systems.

M Weiss

    Biopharmaceutics & Drug Disposition
    |April 1, 1983
    PubMed
    Summary
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    This study introduces a new definition for apparent volume of distribution at steady-state, accounting for real blood concentration variations. It explores how drug elimination impacts this volume using a physiological pharmacokinetic model.

    Area of Science:

    • Pharmacokinetics
    • Physiological modeling
    • Drug distribution

    Background:

    • The apparent volume of distribution is a key pharmacokinetic parameter.
    • Existing definitions may not fully capture intra-circulatory blood concentration heterogeneity.
    • Understanding steady-state distribution is crucial for accurate drug dosing.

    Purpose of the Study:

    • To present a novel definition of the apparent volume of distribution at steady-state.
    • To reconcile this definition with physiological realities of blood concentration gradients.
    • To investigate the influence of drug elimination on steady-state distribution volume.

    Main Methods:

    • Development of a unique definition for apparent volume of distribution at steady-state.
    • Utilization of a physiologically based pharmacokinetic model.

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  • Inclusion of both eliminating and non-eliminating organs within the model.

    • Main Results:

    • The proposed definition aligns with the concept of varying blood concentrations within the circulatory system.
    • The model successfully predicts the impact of drug elimination on the steady-state distribution volume.
    • Demonstrated a unique perspective on drug distribution dynamics.

    Conclusions:

    • The novel definition provides a more realistic representation of drug distribution at steady-state.
    • Physiologically based pharmacokinetic modeling is effective for analyzing drug elimination effects.
    • This work enhances the understanding of drug distribution and its determinants.