Carnitine deficiency and hyperammonemia associated with valproic acid therapy

Plasma carnitine and blood ammonia concentrations were measured in 25 severely handicapped patients, ages 3 to 21 years, and 27 age-matched control subjects. Fourteen of the handicapped patients were treated with anticonvulsant drugs including valproic acid; the remaining 11 patients were treated with drugs excluding valproic acid. Plasma carnitine concentrations were lower and blood ammonia values were higher in patients treated with valproic acid than in the untreated patients and control subjects. A significant inverse relationship was found between plasma carnitine concentrations and the dosage of valproic acid, and between plasma carnitine and blood ammonia values. After oral administration of D,L-carnitine (50 mg/kg/day) for four weeks, both carnitine deficiency and hyperammonemia were corrected.