Influence of ethosuximide on valproic acid serum concentrations

Abstract 

In the therapy of absence epilepsies, a combination of ethosuximide (ESM) and valproic acid (VPA) is sometimes necessary for a successful seizure control. Previous studies of the interaction between ESM and VPA revealed contradictory results. We investigated the influence of ESM on VPA serum concentrations in children with epilepsy. In case of ineffectiveness of the drug, ESM was withdrawn (n=9). Four children treated with VPA got ESM additionally because their seizure control was insufficient with VPA alone. Two children had bromide, and one clobazam as comedicament. Both of these antiepileptic drugs (AEDs) do not have any known interactions with ESM or VPA. Serum levels of VPA were higher in monotherapy than in combination with ESM (120.0±20.1 μg/ml; range, 88.9–153.4 μg/ml; vs. 87.0±13.1 μg/ml; range, 67.4–108.0 μg/ml). The difference was statistically significant (P<0.01). After stopping ESM the serum concentrations of VPA rose about 36.7%; when combined with ESM they fell about 28.3%. Neither the age of the patients nor the serum concentrations of ESM influenced significantly the changes of VPA serum levels in either group. The mechanism of ESM to influence the serum levels of VPA remains unknown. ESM has no known enzyme inducing properties. The interaction of ESM and VPA ought to be considered in a combination therapy of these drugs.

Keywords:  Ethosuximide, Ethosuximide–valproic acid interaction, Bromide, Clobazam