Effect of valproic acid treatment on copper availability in adult epileptic patients.

Objectives: In rats a significant increase of the copper biliary excretion is produced by valproic acid administration, however, a conclusive study on the possible appearance of copper deficiency in humans during treatment with this drug has still not been carried out.

Design And Methods: In 101 adult epileptic patients treated in monotherapy (n=75) and polytherapy (n=26) with valproic acid, and 50 healthy controls, were determined serum copper, immunoreactive ceruloplasmin and its oxidase activity against o-dianisidine, in order to calculate the specific oxidase activity (activity per unit mass of enzyme protein) and copper/ceruloplasmin ratio.

Results: Specific oxidase activity of ceruloplasmin and copper/ceruloplasmin ratio were significantly lower in the groups of patients treated with valproic acid than in the controls. Significant correlations were obtained between both biochemical variables (p<0001). In 38% of the patients treated in mono or polytherapy, the specific oxidase activities of ceruloplasmin were smaller than the estimated lower limit of reference.

Conclusions: These results, possible due to a diminished copper content of the circulating ceruloplasmin, suggest that marginal or moderate copper deficiency may have a substantial prevalence among patients treated with valproic acid.