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Valproate plasma protein binding in the uremic condition

D Brewster, N C Muir

    Clinical Pharmacology and Therapeutics
    |January 1, 1980
    PubMed
    Summary

    Protein binding of sodium valproate is reduced in uremic plasma. Dialysis and charcoal treatment improved binding, suggesting uremic toxins impact drug efficacy.

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    Area of Science:

    • Pharmacokinetics
    • Nephrology
    • Biochemistry

    Background:

    • Sodium valproate is a widely used anticonvulsant medication.
    • Uremia, a syndrome resulting from renal dysfunction, can alter drug pharmacokinetics.
    • Understanding protein binding is crucial for predicting drug efficacy and toxicity.

    Purpose of the Study:

    • To investigate the impact of uremia on sodium valproate protein binding.
    • To explore methods for restoring normal binding capacity in uremic plasma.

    Main Methods:

    • Equilibrium dialysis was used to study protein binding of sodium [carboxy-14C] valproate.
    • Normal and uremic plasma samples were analyzed.
    • Uremic plasma was treated with urea, creatinine, diffusion dialysis, and activated charcoal.

    Main Results:

    • Sodium valproate protein binding was concentration-dependent in both normal and uremic plasma.
    • A significant reduction in binding capacity was observed in uremic plasma compared to normal plasma.
    • Treatment with activated charcoal at pH 3 restored binding capacity to normal levels.
    • Diffusion dialysis partially restored binding, while urea and creatinine caused minor decreases.

    Conclusions:

    • Uremic toxins significantly reduce sodium valproate protein binding.
    • Activated charcoal treatment effectively removes these toxins, restoring normal binding.
    • These findings have implications for optimizing valproate dosing in patients with renal dysfunction.

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