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Related Experiment Videos

Human brain binding of phenytoin.

M A Goldberg, P H Crandall

    Neurology
    |September 1, 1978
    PubMed
    Summary

    Human brain tissue accumulates the anti-epileptic drug phenytoin, suggesting binding to proteins and lipids. This brain uptake occurs against a concentration gradient, with higher levels found in the brain than in cerebrospinal fluid.

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    Area of Science:

    • Neuropharmacology
    • Biochemistry

    Background:

    • Phenytoin is a widely used anti-epileptic drug.
    • Understanding its distribution in the human brain is crucial for optimizing therapy.

    Purpose of the Study:

    • To investigate the binding activity of 3H-phenytoin in human brain tissue.
    • To compare human brain phenytoin binding with animal models.
    • To determine phenytoin levels in human brain, serum, and cerebrospinal fluid (CSF).

    Main Methods:

    • Investigated 3H-phenytoin binding in human brain tissue (biopsy and autopsy samples).
    • Utilized ultrafiltration to assess protein-related binding.
    • Employed partition coefficient technique with hexane to measure lipid interaction.
    • Measured phenytoin concentrations in brain, serum, and CSF.

    Main Results:

    • Phenytoin binding in human brain tissue showed similarities to animal models.
    • Lipid removal enhanced phenytoin binding.
    • Human brain proteins and lipids exhibited lower quantitative activity compared to animals.
    • Human brain phenytoin levels were 4-10 times higher than free drug in CSF.

    Conclusions:

    • Human brain accumulates phenytoin against a concentration gradient.
    • Phenytoin accumulation in the brain is likely mediated by binding to tissue proteins and phospholipids.

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