Concentration-effect relationships of valproic acid

Abstract

Valproic acid is an effective broad spectrum anticonvulsant drug. It has a relatively short half-life, and large diurnal fluctuations in serum concentrations occur, thus making it difficult to define clear relationships between individual serum concentrations and either therapeutic or adverse effects. The value of routine 'one-off' measurements of valproate in clinical practice are further reduced by the absence of a clearly defined dose-related neurotoxicity syndrome. The often quoted therapeutic range for valproate of 50 to 100 mg/L has therefore to be regarded with some circumspection, although available data does suggest an increased incidence of adverse reactions with serum concentrations above 100 mg/L.