The effect of valproate on EEG epileptic abnormalities was investigated at the Institute of Neurophysiology, Genoa, Italy. Sixteen patients aged 14 to 44 years were administered a single (14-37 mg/kg) oral dose of magnesium valproate. At peak serum concentrations of 65-139 ug/ml of valproate, there were increases in spike wave frequency at 2, 3, 4 and 5 hours. The peak concentrations of ammonia ranged from 15-72 ug/1, with values exceeding normal in 13 determinations. The VPA and ammonia concentrations varied independently. The frequency of EEG epileptic abnormalities was not correlated with either the ammonemia level or the amount of variation in ammonemia concentration. [1]

COMMENT. A direct CNS drug action has been proposed to explain the quantitative EEG abnormalities in response to acute VPA administration and the stupor states in some patients. The stupor was not necessarily related to the increased ammonia concentration in the blood.