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Related Experiment Videos

Phenobarbital--valporic acid interaction.

I H Patel, R H Levy, R E Cutler

    Clinical Pharmacology and Therapeutics
    |April 1, 1980
    PubMed
    Summary
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    Valproic acid significantly alters phenobarbital pharmacokinetics. This study found that valproic acid increases phenobarbital

    Area of Science:

    • Pharmacokinetics and Drug Metabolism
    • Clinical Pharmacology
    • Neuropharmacology

    Background:

    • Phenobarbital is a widely used anticonvulsant medication.
    • Valproic acid is another common antiepileptic drug with a different mechanism of action.
    • Potential drug-drug interactions between phenobarbital and valproic acid require investigation.

    Purpose of the Study:

    • To investigate the pharmacokinetic effects of subchronic valproic acid treatment on single-dose phenobarbital kinetics.
    • To determine if valproic acid influences the elimination and metabolism of phenobarbital in healthy subjects.

    Main Methods:

    • A randomized crossover study design was employed in 6 healthy subjects.
    • Subjects received either phenobarbital alone or phenobarbital after 14 days of valproic acid administration.

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  • Plasma and urine samples were collected over 12 days and analyzed using gas chromatography-mass spectrometry (GC-MS).

    • Main Results:

    • Valproic acid significantly increased phenobarbital half-life (96 to 142 hr) and decreased plasma clearance (4.2 to 3.0 ml/hr/kg).
    • Metabolic clearance of phenobarbital was reduced by valproic acid (3.3 to 2.0 mg/hg/kg), while renal clearance remained unchanged.
    • The fraction of phenobarbital excreted unchanged increased, indicating reduced metabolism.

    Conclusions:

    • Valproic acid inhibits the metabolism of phenobarbital.
    • This interaction may necessitate dosage adjustments when co-administering these two drugs.
    • Further clinical studies are warranted to confirm these findings in patient populations.