Valproate-induced hyperammonemia.

A patient with carbamyl phosphate synthetase deficiency had four episodes of hyperammonemia, up to 226 microM, associated with valproate (VPA) treatment. These were accompanied by vomiting, lethargy, and coma. A group of epileptic patients receiving VPA remained asymptomatic but had significantly higher mean plasma ammonium levels when compared to epileptic patients receiving other anticonvulsants: 33.6 +/- 1.9 (SEM) versus 23.6 +/- 1.5 microM. Thus, VPA caused symptomatic hyperammonemia in a patient with an impairment in urea synthesis and resulted in mildly elevated ammonium levels in epileptic patients. These data suggest that ammonium levels should be monitored in patients receiving VPA who exhibit signs of vomiting or lethargy.