Selenium, zinc, and copper changes with valproic acid: possible relation to drug side effects

Side effects of treatment with the anticonvulsant valproic acid (VPA) suggested the possibility of alteration of trace metal status. Administration of VPA for 1 week produced significant depletion of zinc and selenium in plasma of rats and a one-third reduction of hepatic selenium. Patients who were treated chronically, with VPA as the sole anticonvulsant medication, had decreased plasma selenium levels. Most cases of VPA-associated hepatotoxicity occur in children. This could be due to decreased selenium concentrations when mechanisms for protection against peroxidative damage are not fully developed.