Hepatotoxicity of sodium valproate and other anticonvulsants in rat hepatocyte cultures.
Valproic acid has recently been shown to be associated with liver disease in man. Rat hepatocyte cultures were used to test the hepatotoxicity of valproic acid and several other anticonvulsants. Dose-related hepatotoxicity was demonstrated for valproic acid at concentrations ranging from 10 to 320 micrograms/ml, therapeutic concentrations being 50-100 micrograms/ml. Hepatotoxicity could not be demonstrated for phenobarbital, phenytoin, primidone, and clonazepam. It is concluded that valproic acid is a dose-related hepatotoxin.
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D002998:Clonazepam / Q000009:adverse effects; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D010634:Phenobarbital / Q000009:adverse effects; D010672:Phenytoin / Q000009:adverse effects; D011324:Primidone / Q000009:adverse effects; D051381:Rats; D014635:Valproic Acid / Q000009:adverse effects*
D000927:Anticonvulsants; D011324:Primidone; D002998:Clonazepam; D014635:Valproic Acid; D010672:Phenytoin; D007770:L-Lactate Dehydrogenase; D010634:Phenobarbital