Plasma total, free, and acyl carnitine levels were determined in children treated with valproic acid at the Valley Children’s Hospital and University of California, San Francisco, Fresno, CA. The mean total carnitine level was significantly lower in patients given valproic acid polytherapy compared with normal subjects and with those receiving valproic acid monotherapy. The levels in both the valproic acid monotherapy and polytherapy groups were significantly lower than those treated with other antiepileptic drugs. The mean free carnitine level was significantly lower in both the valproic acid monotherapy and polytherapy groups compared to normal subjects and the other antiepileptic drug group. Acylcarnitine levels were also lower in the polytherapy valproic acid group compared to the monotherapy valproic acid group and those receiving other antiepileptic drugs. The study indicates that a general decrease in the carnitine pool should be anticipated in patients taking valproic acid polytherapy and to a lesser degree, monotherapy. [1]
COMMENT. Plasma and erythrocyte carnitine was significantly lower in 37 children on sodium valproate alone or in combination with other drugs compared to levels in 22 children on drugs other than sodium valproate in a study from the Royal Aberdeen Children’s Hospital, University of Aberdeen, Scotland [2]. Plasma ammonia was also elevated in the valproate group. Urinary free carnitine was reduced in valproate treated children with a significant increase in the ratio of bound to free carnitine. Carnitine supplementation is recommended.
Alterations of renal carnitine metabolism by valproic acid were studied in mice at the University of Santiago de Compostela, Spain [3]. Valproic acid induced a significant increase in renal clearance of acylcarnitine without affecting that of free carnitine, whereas other anticonvulsants increased clearance of free carnitine but not that of acylcarnitine.
Erratum. We thank Dr. J.M. Prats, Hospital de Cruces, Bilbao, Spain, for the correction of an error in the article concerning sodium valproate treatment of infantile spasms reviewed in Ped Neur Briefs Aug 1991; 5:63. The sentence should read as follows: “The hypsarrythmia EEG pattern was controlled after two weeks treatment with VPA 100 to 300 mg/Kg/daily in 80% of patients.”