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Changes in protein binding during disease.

W A Craig, B Suh

    Scandinavian Journal of Infectious Diseases. Supplementum
    |January 1, 1978
    PubMed
    Summary
    This summary is machine-generated.

    Disease states significantly impact antimicrobial protein binding through altered serum protein levels or accumulated compounds like bilirubin and free fatty acids (FFA). These changes affect drug distribution and assay results.

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    Area of Science:

    • Pharmacology
    • Clinical Chemistry
    • Microbiology

    Background:

    • Disease states can alter antimicrobial protein binding.
    • This alteration is due to changes in serum protein concentration or accumulation of endogenous compounds like bilirubin and free fatty acids (FFA).

    Purpose of the Study:

    • To investigate how disease states affect antimicrobial protein binding.
    • To understand the impact of altered protein concentrations and endogenous compounds on drug-protein interactions.

    Main Methods:

    • In vitro studies involving addition of bilirubin and FFA to normal serum.
    • Analysis of patient sera from individuals with hyperbilirubinemia and during heparin administration.
    • Investigation of antimicrobial binding in uremic patient sera.

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    Main Results:

    • Marked reduction in antimicrobial binding occurs only at extremely low albumin levels (<2.5 m/100 ml).
    • High concentrations of bilirubin and FFA reduce binding of most antimicrobials in vitro.
    • Some antibiotics show enhanced binding at lower FFA concentrations, potentially via allosteric mechanisms.
    • Reduced binding in uremia may involve an unknown endogenous inhibitor.
    • In vitro findings are corroborated by in vivo patient data.

    Conclusions:

    • Disease-induced alterations in serum proteins and endogenous compounds significantly affect antimicrobial protein binding.
    • These changes can influence drug distribution and the accuracy of microbiologic assays.
    • Further research is needed to identify the endogenous inhibitor present in uremia.