Valproate metabolite concentrations in brain increase with chronic administration of sodium valproate.

Rats were treated chronically with sodium valproate for varying periods of time up to eight weeks. A statistically significant negative correlation between plasma concentrations of valproate-derived substances (VDS) and length of treatment was observed while a statistically significant positive correlation was found between brain VDS concentration and length of treatment. Liver VDS concentrations showed a tendency to decrease with time but this trend was not statistically significant. A new procedure was developed to measure the tissue levels of VDS.