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Variability in the human drug response.

G D Sweeney

    Thrombosis Research. Supplement
    |January 1, 1983
    PubMed
    Summary

    Drug response variability arises from pharmacodynamic or pharmacokinetic differences. While pharmacodynamic variations are less understood clinically, pharmacokinetic factors like absorption and metabolism significantly impact drug concentrations and therapeutic outcomes.

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    Area of Science:

    • Pharmacology
    • Drug Metabolism and Pharmacokinetics

    Background:

    • Individual responses to medications vary due to pharmacodynamic (receptor sensitivity) or pharmacokinetic (drug concentration) factors.
    • Both inherited and acquired variations can influence drug response, but clinical relevance is often better documented for pharmacokinetic differences.

    Purpose of the Study:

    • To explore the origins of inter-individual variability in drug response.
    • To highlight the importance of pharmacokinetic factors and the limitations of current models in predicting drug variability.

    Main Methods:

    • Review of existing literature on pharmacodynamic and pharmacokinetic variations in drug response.
    • Analysis of common pharmacokinetic models and their predictive capabilities.

    Main Results:

    • Pharmacokinetic variations, including those related to drug formulation, absorption, distribution, metabolism, and excretion, are well-described causes of differing drug concentrations.
    • Current pharmacokinetic models may not accurately predict variability due to their failure to represent physiological variables and events like macromolecular binding or altered blood flow.

    Conclusions:

    • Pharmacokinetic variability is a significant factor influencing drug efficacy, especially when drug concentration is critical.
    • Improved pharmacokinetic models that incorporate physiological variables and emphasize unbound drug concentrations are needed for accurate prediction of drug response variability.

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