Affiliation:
1. Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China
2. Department of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, China
3. Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, United States
Abstract
Background:
Valproic acid (VPA) as a widely used primary medication in the treatment of epilepsy is
associated with reversible or irreversible hepatotoxicity. Long-term VPA therapy is also related to increased risk
for the development of non-alcoholic fatty liver disease (NAFLD). In this review, metabolic elimination pathways
of VPA in the liver and underlying mechanisms of VPA-induced hepatotoxicity are discussed.
Methods:
We searched in PubMed for manuscripts published in English, combining terms such as “Valproic
acid”, “hepatotoxicity”, “liver injury”, and “mechanisms”. The data of screened papers were analyzed and summarized.
Results:
The formation of VPA reactive metabolites, inhibition of fatty acid β-oxidation, excessive oxidative
stress and genetic variants of some enzymes, such as CPS1, POLG, GSTs, SOD2, UGTs and CYPs genes, have
been reported to be associated with VPA hepatotoxicity. Furthermore, carnitine supplementation and antioxidants
administration proved to be positive treatment strategies for VPA-induced hepatotoxicity.
Conclusion:
Therapeutic drug monitoring (TDM) and routine liver biochemistry monitoring during VPA-therapy,
as well as genotype screening for certain patients before VPA administration, could improve the safety profile of
this antiepileptic drug.
Funder
Science and Technology Development Foundation of Nanjing Medical University
Natural Science Foundation of Jiangsu Province
National Natural Science Foundation of China
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
Cited by
61 articles.
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