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Phenytoin binding to human albumin.

M Lecomte, R Zini, P d'Athis

    European Journal of Drug Metabolism and Pharmacokinetics
    |January 1, 1979
    PubMed
    Summary

    Phenytoin primarily binds to human serum albumin, with binding unaffected by drug concentration. Other acidic substances can reduce phenytoin binding, indicating potential drug interactions.

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    Area of Science:

    • Pharmacokinetics
    • Biochemistry
    • Drug Metabolism

    Background:

    • Phenytoin is an anticonvulsant drug with a narrow therapeutic index.
    • Understanding phenytoin's protein binding is crucial for optimizing its efficacy and safety.
    • Human serum albumin is a primary binding protein for many drugs in circulation.

    Purpose of the Study:

    • To investigate the binding characteristics of phenytoin to human plasma proteins, specifically human serum albumin.
    • To determine the affinity and number of binding sites for phenytoin on albumin.
    • To explore the influence of other substances on phenytoin-albumin interactions.

    Main Methods:

    • Equilibrium dialysis was employed to study drug binding.
    • Experiments were conducted at physiological conditions (pH 7.4 and 37°C).
    • The effects of co-administered substances (palmitic acid, warfarin, phenylbutazone, basic, and non-ionizable drugs) were assessed.

    Main Results:

    • Phenytoin predominantly binds to human serum albumin.
    • Binding percentage remained constant across varying total drug concentrations.
    • Low affinity (k = 745 M⁻¹) and a high number of binding sites (n = 8) were calculated.
    • Palmitic acid, warfarin, and phenylbutazone non-competitively inhibited phenytoin binding.
    • Basic and non-ionizable drugs did not affect phenytoin binding.

    Conclusions:

    • Phenytoin exhibits saturable binding to human serum albumin with a high capacity.
    • Co-administration with certain acidic drugs or fatty acids may alter phenytoin's free fraction.
    • These findings highlight the importance of considering drug-drug interactions affecting protein binding for phenytoin therapy.

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