The Toxicity of Metabolites of Sodium Valproate in Cultured Hepatocytes
- 1 April 1983
- journal article
- Published by Wiley in The Journal of Clinical Pharmacology
- Vol. 23 (4), 178-185
- https://doi.org/10.1002/j.1552-4604.1983.tb02722.x
Abstract
Sodium valproate is hepatotoxic in both humans and rat hepatocytes. The toxicity is dose related and frequently associated with simultaneous ingestion of drugs which induce the drug metabolizing system. For these reasons, metabolites of sodium valproate were tested for toxicity using rat hepatocyte cultures. The sodium salts of three metabolites, 2‐propylpent‐4‐enoate, 4‐hydroxyvalproate, and perhaps 5‐hydroxyvalproate, were toxic in this system. In addition, 2‐propylpent‐4‐enoate was toxic in a dose‐related fashion. All are ω and ω‐1 oxidation products in the microsome‐mediated pathway of valproate metabolism.Keywords
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