Valproic acid—induced hyperammonemic encephalopathy in a full-term neonate: a brief review and case report

Introduction
Valproic acid (2-propylvaleric dipropyl acetic acid, VPA), the free acid form of sodium valproate, is used as a third-line drug in the management of neonatal seizures. VPA dosing in neonates, and pharmacokinetics (PK) of VPA and other anticonvulsive drugs (AEDs) are reported in a systematic review based on 19 PK studies (7 AEDs). However, prospective randomized control studies are not performed. Therapeutic plasma concentrations of VPA (CplVPA) range from 50 to 100 mg/L (347–750 μmol/L), 5–18% correspond with a free VPA fraction. Toxic CplVPA and/or VPA-metabolites may lead to VPA-induced hyperammonemic encephalopathy and VPA-induced hepatotoxicity mainly in young infants. There are several mechanisms of VPA-induced hyperammonemia, but no data are available in neonates. However, in 50% of neonates, VPA-induced hyperammonemia results in discontinuation of therapy.