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On pharmacokinetics in target tissues.

M Weiss

    Biopharmaceutics & Drug Disposition
    |January 1, 1985
    PubMed
    Summary
    This summary is machine-generated.

    This study models drug exposure in target tissues, revealing that total exposure depends on partition coefficients, while residence time is influenced by membrane permeability. These factors inform strategies for optimal drug delivery and therapeutic ratios.

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    Area of Science:

    • Pharmacokinetics and Drug Metabolism
    • Physiological Modeling
    • Quantitative Systems Pharmacology

    Background:

    • Understanding drug disposition in target tissues is crucial for optimizing therapeutic efficacy and minimizing toxicity.
    • Quantitative models are essential for predicting drug concentration-time profiles within organs.

    Purpose of the Study:

    • To evaluate total drug exposure, mean tissue residence time, and peak tissue concentration using a two-compartment organ model.
    • To elucidate the influence of drug properties (partition coefficient, permeability) and organ characteristics (volume, blood flow) on pharmacokinetic parameters.
    • To define a tissue-specific therapeutic ratio and discuss the advantages of local drug administration.

    Main Methods:

    • Development and application of a two-compartment organ model.

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  • Analysis of drug parameters including tissue-to-blood partition coefficient and permeability coefficient (membrane permeability).
  • Inclusion of organ-specific parameters such as organ volume and blood flow.

    • Main Results:

    • Total drug exposure is primarily dependent on the tissue-to-blood partition coefficient.
    • Mean tissue residence time is influenced by both the partition coefficient and the permeability coefficient.
    • Peak tissue concentration is mainly determined by mean organ transit time and the blood concentration profile.

    Conclusions:

    • The study provides a quantitative framework for understanding drug exposure and residence time in target tissues.
    • A tissue-specific therapeutic ratio can be defined based on total exposure, guiding drug development.
    • Local routes of drug administration may offer advantages for achieving desired therapeutic ratios by modulating exposure and residence time.