A randomized controlled trial of initial Valproic acid dosage in epileptic children / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate whether the population pharmacokinetics (PPK)models can optimize the initial dosage of individualized Valproic acid (VPA)in children with epilepsy. Methods The epileptic children without taking VPA previously were recruited from October 2015 to May 2017 at the Department of Pediatrics,Peking University First Hospital,and they were divided into the PPK model group and the traditional empirical method group by randomized method. The initial VPA dosages for the PPK model group were calculated by PPK model,whereas those of the traditional empirical method group were dosed at 20-25 mg/(kg·d)regularly. The steady-state serum trough concentrations of VPA were extracted,and then the number and percentage of the patients whose serum trough concen-trations of VPA were 50-100 mg/L in the 2 groups were analyzed and compared with prospectively randomized me-thod. Results Totally 65 epileptic children were recruited and they were randomly divided into the traditional empirical method group (32 cases)and the PPK model group (33 cases). Twenty-seven children in the traditional empirical method group were observed,and 12 children had local epilepsy attack and 15 had generalized seizures;whereas among 29 cases in the PPK model group,there were 12 local attack of epilepsy and 17 had generalized seizures. VPA add-on therapy was administrated in 9 cases and 15 cases in the traditional empirical method group and the PPK model group, respectively. There were 5 cases,21 cases and 1 case with VPA serum concentrations of ＜50 mg/L,50-100 mg/L and＞100 mg/L in the traditional empirical group;while there were 9 cases,20 cases and 0 case in the PPK model group. The VPA serum concentrations of 21 cases (77. 8%,21/27 cases)in the traditional empirical method group and 20 ca-ses (69. 0%,20/29 cases)in the PPK model group were 50-100 mg/L,respectively,and the difference was not sta-tistically significant(P＞0. 05). Conclusion Although the study doesn't suggest that the established PPK model of VPA in Chinese epileptic children is superior to the traditional empirical method,the PPK model might be potentially valuable for optimized individualized dosage adjustment for those with serum trough concentrations not in the reasonable range by the traditional empirical method and with clinical seizure or brain firing activities.