Evidence for a potential protective effect of carnitine-pantothenic acid co-treatment on valproic acid-induced hepatotoxicity.
Valproic acid is approved for treatment of seizures and manic episodes of bipolar disorder, and continues to be one of the most commonly prescribed antiepileptic drugs in the world. Hepatotoxicity is a rare but serious side effect resulting from its use, particularly in young patients. This adverse effect does not display normal dose-response curves and can be lethal in children. A review of the purported mechanisms of action suggest hepatotoxicity results from increased oxidative stress, caused by a reduction in beta-oxidation and an increase in activation of certain metabolizing enzymes. There is also evidence that both carnitine and pantothenic acid are involved in the regulation of valproic acid-induced hepatotoxic processes, and clinical evidence has shown that treatment with either compound shows protective effects against hepatotoxicity. These results suggest a potential increase in protective effects with cotreatment of carnitine and pantothenic acid.
University of California, Berkeley, Morgan Hall, Berkeley, CA 94720-3104, USA.
Dana
D
Felker
Alexandra
A
Lynn
Sue
S
Wang
Dale E
DE
Johnson
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy; D002331:Carnitine / Q000008:administration & dosage / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control*; D002648:Child; D004359:Drug Therapy, Combination; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010205:Pantothenic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
D000927:Anticonvulsants; D010205:Pantothenic Acid; D014635:Valproic Acid; D002331:Carnitine