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Related Experiment Videos

Diurnal variation in valproic acid clearance.

L A Bauer, R Davis, A Wilensky

    Clinical Pharmacology and Therapeutics
    |April 1, 1984
    PubMed
    Summary

    Valproic acid levels in the body fluctuate throughout the day, with higher concentrations in the morning. To ensure accurate monitoring of valproic acid (VPA) levels, blood samples should be collected at consistent times.

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    Area of Science:

    • Pharmacokinetics
    • Clinical Chemistry

    Background:

    • Valproic acid (VPA) is a widely used antiepileptic drug.
    • Understanding diurnal variations in VPA concentrations is crucial for therapeutic drug monitoring.

    Purpose of the Study:

    • To investigate the diurnal variation in total and unbound valproic acid concentrations at steady state.
    • To assess the impact of time of day on VPA pharmacokinetic parameters.

    Main Methods:

    • Seven healthy men and three healthy women received 250-mg oral doses of VPA every 12 hours.
    • Total and unbound VPA concentrations were measured at steady state.
    • Pharmacokinetic parameters, including clearance and time to peak concentration, were analyzed.

    Main Results:

    • Higher total and unbound VPA concentrations were observed during the morning dosage interval compared to the evening.
    • Total average steady-state concentrations (Css) were 50.4 mg/l (morning) and 45.7 mg/l (evening).
    • Increased total and unbound VPA clearance rates were noted during the evening dosage interval, leading to lower concentrations.

    Conclusions:

    • Significant diurnal variation exists in total and unbound valproic acid concentrations.
    • Higher clearance rates in the evening contribute to lower VPA levels.
    • Consistent timing of blood draws is recommended for reproducible VPA concentration measurements.

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