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Updated: Aug 13, 2026

Interictal High Frequency Oscillations Detected with Simultaneous Magnetoencephalography and Electroencephalography as Biomarker of Pediatric Epilepsy
10:22

Interictal High Frequency Oscillations Detected with Simultaneous Magnetoencephalography and Electroencephalography as Biomarker of Pediatric Epilepsy

Published on: December 6, 2016

Valproic acid free fraction in epileptic children under chronic monotherapy

R Riva, F Albani, E Franzoni

    Therapeutic Drug Monitoring
    |June 1, 1983
    PubMed

    Insights

    Free valproic acid (VPA) levels in epileptic children are lower in the early morning. This diurnal variation in VPA concentration may impact therapeutic drug monitoring and requires consideration during treatment.

    Area of Science:

    • Pharmacology
    • Clinical Pharmacy
    • Pediatric Neurology

    Background:

    • Valproic acid (VPA) is a widely used antiepileptic drug.
    • Understanding VPA pharmacokinetics, including diurnal variations, is crucial for effective treatment.

    Purpose of the Study:

    • To investigate the diurnal variation of total and free valproic acid concentrations in epileptic children.
    • To explore the relationship between total VPA concentration, free fraction, and time of day.

    Main Methods:

    • Plasma samples were collected from 62 epileptic children on sodium valproate monotherapy.
    • Samples were analyzed for total and free VPA concentrations before the morning dose and 3 hours later.
    • Statistical analysis was used to compare concentrations and correlate findings.

    Main Results:

    • Both total and free VPA concentrations were significantly lower in early morning samples compared to late morning samples.
    • The free fraction of VPA was also lower in the early morning.
    • A positive correlation was observed between free fraction and total VPA concentration at both sampling times.

    Conclusions:

    • Diurnal variations in plasma VPA concentrations exist in epileptic children.
    • Higher free fatty acid levels after fasting may contribute to lower free VPA fractions in the early morning.
    • These findings have implications for optimizing therapeutic drug monitoring of VPA.

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