Epileptic child in remission: Ceiling effect of valproic acid

Therapeutic drug monitoring (TDM) of valproic acid (VPA) for epileptic children aims to optimize treatment, hence promoting seizure control, and to detect refractory cases that should be managed early. We aimed to identify a ceiling dose and a trough serum level of VPA in epileptic children in remission.

This retrospective study was carried out at Clinical Pharmacology, involving epileptic children (2-18 years) who were referred at least two times for a VPA trough level measurement over a 13-year period (2009-2022).

We included 88 children, of whom 67% (n=59) were in remission (G1) and 33% (n=29) did not meet remission criteria (G2). Ten children (11%) experienced adverse events, predominantly gastrointestinal and neuropsychological disturbances. Mean weight-based dose of VPA in G1 (21.53±7.95 mg/kg/day) was significantly lower than in G2 (26.81±9.99 mg/kg/day), p=0.009. Mean VPA trough serum level was 60.76±20.22 µg/mL in G1 and 62.47±23.04 µg/mL in G2 with no significant difference. The ceiling daily dose of VPA to achieve remission was 44.44 mg/kg/day.

Our study showed that the average weight-based dose of VPA in children in remission was lower than that in G2. A ceiling dose of 44.44 mg/kg/day of VPA limiting treatment efficacy for achieving remission was identified.