A comparative clinical and pharmacokinetic study of a new slow-release versus conventional preparations of valproic acid in children with intractable epilepsy.

Thirteen children with intractable epilepsy were treated by means of three-times-daily administration of a conventional preparation of valproic acid (C-VPA) and twice-daily administration of a new slow-release preparation of VPA (SR-VPA) with the cross-over technique. The frequency of seizures, side effect and steady-state pharmacokinetics of VPA were evaluated. With the change from C-VPA tid to SR-VPA bid, four patients exhibited a significant reduction in seizure frequency. The steady-state minimum concentration (Cmin) was higher, the maximum concentration (Cmax) lower and there were less diurnal fluctuations with SR-VPA, than with the respective values obtained in the C-VPA group, all the differences being statistically significant. Furthermore, a significant difference was unexpectedly found in the area under the curve (AUC) from 0 to 24 hours, the mean AUC in the period of SR-VPA being 9% higher than that with C-VPA. Five of the nine patients under 6 years of age showed more than 10% increase, and all four patients over 6 years of age less than 10% increase or a decrease in AUC. It was concluded that with SR-VPA bid, the pharmacokinetic features were more stable, the age-related AUC value was larger and the clinical effect was better than in comparison to C-VPA tid in children with intractable epilepsy.