Valproic Acid and the Liver Injury in Patients with Epilepsy: An update
作者单位：Department of Pharmacy Children's Hospital of Nanjing Medical University School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University Department of Pharmacology University of Tennessee Health Science Center
会议名称：《第八届全国治疗药物监测学术年会》
会议日期：2018年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
关 键 词：Valproic acid antiepileptic treatment liver injury management glucuronic acid conjugation β-oxidation oxidative stress genetic variants
摘 要：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 *** 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 become positive treatment strategies for VPA-induced *** drug monitoring（TDM） and routine liver biochemistry monitoring during VPA-therapy, as well as genotype screening for certain patients before VPA administration, couldimprove the safety profile of this antiepileptic drug.