title: Simultaneous determination of valproic acid and 2-propyl-4-pentenoic acid for the prediction of clinical adverse effects in Chinese patients with epilepsy.
abstract: 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: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road, Section 2, Guangzhou 510080, China.
authors: Zhuo-Jia
authors: ZJ
authors: Chen
authors: Xue-Ding
authors: XD
authors: Wang
authors: Hong-Sheng
authors: HS
authors: Wang
authors: Shu-da
authors: SD
authors: Chen
authors: Lie-Min
authors: LM
authors: Zhou
authors: Jia-Li
authors: JL
authors: Li
authors: Wen-Ying
authors: WY
authors: Shu
authors: Jue-Qian
authors: JQ
authors: Zhou
authors: Zi-Yan
authors: ZY
authors: Fang
authors: Yu
authors: Y
authors: Zhang
authors: Min
authors: M
authors: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood* / Q000737:chemistry; D002648:Child; D002681:China; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005229:Fatty Acids, Monounsaturated / Q000097:blood* / Q000737:chemistry; D005260:Female; D006801:Humans; D007492:Iran; D008297:Male; D014481:United States; D014635:Valproic Acid / Q000009:adverse effects* / Q000097:blood* / Q000737:chemistry; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D005229:Fatty Acids, Monounsaturated; C045022:2-propyl-4-pentenoic acid; D014635:Valproic Acid