Free and Total Serum Valproate Concentrations: Their Relationship to Seizure Control, Liver Enzymes and Plasma Ammonia in Children

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Abstract
The relationships between total and free serum valproate (VPA) concentrations and seizure control, serum liver enzyme activity and plasma ammonia concentration were studied in 61 epileptic children. Enzymeimmunoassay (EMIT)Rmethods gave higher values of total VPA concentration than gas-liquid chromatography (GLC) methods. In over 80% of children with complete seizure control the ranges of total VPA concentration were 140-420 umol/L with GLC methods and 210-560 umol/L with EMIT methods. The range of free VPA concentrations in 78% of children with complete seizure control was 8.8-26.4 umol/L. Increased liver enzyme activity was observed in 6 of the 61 children and raised plasma ammonia concentration in 11 of 50 children. Plasma ammonia concentration was related to total serum VPA but was not related to free serum VPA. Increased serum liver enzyme activity was related to VPA dose per kg but not to free or total serum VPA concentration. Thus free VPA concentrations do not appear to be more useful than total VPA concentrations in predicting seizure control and do not correlate with liver enzyme activity or plasma ammonia concentration.