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Percutaneous absorption in man: a kinetic approach.

R H Guy, J Hadgraft, H I Maibach

    Toxicology and Applied Pharmacology
    |March 30, 1985
    PubMed
    Summary

    A new biophysical model predicts chemical absorption through human skin. This model uses four rate constants to estimate skin penetration and urinary excretion, aiding in understanding chemical exposure risks.

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    Area of Science:

    • Pharmacokinetics
    • Dermal Absorption
    • Biophysical Modeling

    Background:

    • Human skin acts as a barrier to chemical absorption.
    • Understanding chemical penetration kinetics is crucial for risk assessment.

    Purpose of the Study:

    • To develop and apply a biophysically based kinetic model for chemical absorption through human skin.
    • To estimate penetration kinetics for 12 diverse chemicals.

    Main Methods:

    • A linear pharmacokinetic model with four first-order rate constants (k1-k4) was employed.
    • k1 and k2 were estimated using diffusion coefficients and molecular weight.
    • k3 was optimized by fitting urinary excretion data, reflecting stratum corneum affinity.
    • k4 values were experimentally determined.

    Main Results:

    • The model successfully simulated urinary excretion rates for 12 chemicals.
    • Estimated k3/k2 ratios correlated well with octanol-water partition coefficients.
    • This suggests the model captures the chemical's affinity for the stratum corneum.

    Conclusions:

    • The developed model provides a framework for predicting percutaneous absorption kinetics.
    • Chemical molecular weight and lipophilicity are key factors in skin penetration.
    • This approach has potential for assessing dermal exposure risks.

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