What question did this study set out to answer?

To evaluate the relationship between trough serum valproic acid levels and clinical responses in epileptic patients on stable monotherapy.

March 16, 2026Open Access

Therapeutic Drug Monitoring of Valproic Acid: A Cross-Sectional Correlation Study between Serum Levels and Clinical Response in Epileptic Patients

Key Points

To evaluate the relationship between trough serum valproic acid levels and clinical responses in epileptic patients on stable monotherapy.
Conducted a prospective cross-sectional observational study over 12 months.
Enrolled 100 adults aged 18-60 on stable sodium valproate monotherapy for at least 4 weeks.
Collected trough blood samples 12 hours after dosing and measured VPA concentrations using HPLC-UV.
Classified serum levels as sub-therapeutic, therapeutic, or toxic and assessed seizure control classification.
Used Pearson correlation to examine relationships between serum levels and clinical outcomes.
Mean serum valproic acid level was 72.5 ± 23.4 µg/mL, with 20% sub-therapeutic, 65% therapeutic, and 15% toxic levels.
Complete seizure control was noted in 61%, mean VPA level of 79.2 ± 20.3 µg/mL; partial control in 26% at 68.4 ± 22.5 µg/mL; uncontrolled in 13% at 51.7 ± 19.6 µg/mL.
A significant correlation was found between serum VPA concentration and clinical outcomes (r = 0.42, p = 0.002).
Adverse drug reactions occurred in 19%, primarily tremor (7%) and weight gain (6%).

Abstract

Abstract Background: Valproic acid (VPA) is a widely used broad-spectrum antiepileptic drug, but inter individual pharmacokinetic variability can lead to inconsistent seizure control and adverse effects at similar doses. Therapeutic drug monitoring (TDM) may help optimize therapy by correlating serum drug concentrations with clinical response. Objective: To estimate trough serum VPA levels in epileptic patients receiving valproate monotherapy and determine their correlation with seizure control and adverse drug reactions (ADRs). Methods: A prospective cross-sectional observational study was conducted over 12 months in the Departments of Pharmacology and Neurology, JLN Medical College, Ajmer, Rajasthan. One hundred adults (18–60 years) with epilepsy on stable sodium valproate monotherapy for ≥4 weeks were enrolled. Trough blood samples were collected 12 hours post-dose, serum was stored at −20°C, and VPA concentrations were measured using HPLC-UV. Serum levels were categorized as sub-therapeutic (100 µg/mL). Seizure control over the preceding three months was classified as complete, partial, or uncontrolled. Pearson correlation assessed relationships between serum levels and clinical variables. Results: Mean age was 34.8 ± 10.2 years; 58% were male; GTCS was the commonest seizure type (72%). Mean serum VPA level was 72.5 ± 23.4 µg/mL; 20% were sub-therapeutic, 65% therapeutic, and 15% toxic. Complete seizure control was achieved in 61% (mean VPA 79.2 ± 20.3 µg/mL), partial control in 26% (68.4 ± 22.5 µg/mL), and uncontrolled seizures in 13% (51.7 ± 19.6 µg/mL). Serum VPA concentration correlated significantly with clinical outcome (r = 0.42, p = 0.002), while correlations with dose (r = 0.18, p = 0.07) and duration of therapy (r = 0.09, p = 0.32) were not significant. ADRs occurred in 19%, most commonly tremor (7%) and weight gain (6%). Conclusion: Serum VPA trough concentration showed a significant positive association with seizure control and was a better predictor of response than prescribed dose. Routine TDM can support individualized dosing to improve efficacy and reduce toxicity in epilepsy management.

Therapeutic Drug Monitoring of Valproic Acid: A Cross-Sectional Correlation Study between Serum Levels and Clinical Response in Epileptic Patients

Key Points

Abstract

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