Document Detail


Simultaneous determination of valproic acid and 2-propyl-4-pentenoic acid for the prediction of clinical adverse effects in Chinese patients with epilepsy.
MedLine Citation:
PMID:  22055352     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Valproic acid (VPA) is a well-established anticonvulsant drug that has been increasingly used in the treatment of many forms of generalized epilepsy. Although there are many reports of adverse effects of VPA, studies focusing on the concentration-response relationships of VPA and its metabolites in patients with epilepsy are extremely limited. In this study, a rapid and specific high performance liquid chromatography-ultraviolet (HPLC-UV) method to simultaneously detect the concentrations of VPA and its major hepatotoxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in human plasma has been established, using 2,4'-dibromoacetophenone and octanoic acid as the derivatization reagent and internal standard, respectively. This method was used to analyze plasma samples (n=64) of Chinese patients with epilepsy. The results revealed that 4-ene VPA concentrations in Chinese patients were much higher than those in patients in other countries such as United States and Iran. Significant correlations between aspartate aminotransferase (AST), alanine aminotransferase (ALT) and 4-ene VPA concentration suggest that the simultaneous determination of VPA and 4-ene VPA is an effective tool for the prediction of clinical hepatotoxicity in epileptic patients. Furthermore, the present study describes a less costly and complex technique for the clinical monitoring of VPA plasma levels and the risk of hepatotoxicity which may be of particular interest in developing countries like China.
Authors:
Zhuo-Jia Chen; Xue-Ding Wang; Hong-Sheng Wang; Shu-da Chen; Lie-Min Zhou; Jia-Li Li; Wen-Ying Shu; Jue-Qian Zhou; Zi-Yan Fang; Yu Zhang; Min Huang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-3
Journal Detail:
Title:  Seizure : the journal of the British Epilepsy Association     Volume:  -     ISSN:  1532-2688     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306979     Medline TA:  Seizure     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road, Section 2, Guangzhou 510080, China.
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