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


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.
Lampón
Natalia
N
Unidad Monitorización Fármacos, Laboratorio Central, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain.
Tutor
J Carlos
JC
D000328:Adult; D000927:Anticonvulsants; D016022:Case-Control Studies; D002570:Ceruloplasmin / Q000032:analysis / Q000378:metabolism; D003300:Copper / Q000097:blood* / Q000172:deficiency*; D004827:Epilepsy / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D014635:Valproic Acid; D003300:Copper; D002570:Ceruloplasmin