Valproic acid-induced hepatotoxicity and protective role of carnitine

ABSTRACT

Valproic acid [valproate; VPA] is a first line drug for use in epilepsy. Often the handicapped/ epileptic children are undernourished in developing countries. Valproic acid reduces serum carnitine which is an essential cofactor in transport of long chain fatty acids across the inner mitochondrial membrane. Low serum carnitine and malnourishment can cause fatty infiltration and hepatotoxicity leading to a Reye-like syndrome and/or fulminant hepatic failure. In an experimental study on rats treated with therapeutic/toxic doses of valproic acid supplemented by carnitine, we have found that valproic acid alone caused fatty infiltration and necrosis of the liver while carnitine supplementation prevented these events. It is suggested that valproic acid therapy be supplemented with canitine in epileptic patients and liver function profile must be regularly monitored in these patients. Adequate intake of carnitine must be ensured in growing infants and children