Acute changes of blood ammonia may predict short-term adverse effects of valproic acid.

Valproic acid (VPA) was given to 24 epileptic patients who were already being treated with other antiepileptic drugs. A standardized loading dose of VPA was administered, and venous blood was sampled at 0, 1, 2, 3, and 4 hours. Ammonia (NH3) was higher in patients who, during continuous therapy, complained of drowsiness (7 patients) than in those who were symptom-free (17 patients), although VPA plasma levels were similar in both groups. By measuring VPA-induced changes of blood NH3 content, it may be possible to identify patients at higher risk of obtundation when VPA is given chronically.