丙戊酸钠及其代谢产物与肝损伤的相关性分析

Correlation analysis of valproic acid and its metabolites to hepatotoxicity

目的研究丙戊酸钠及3个代谢产物(2-丙基-4-五烯酸、3-羟基丙戊酸、5-羟基丙戊酸)对肝损伤参考指标的相关性分析。方法共收集328例癫痫患者血样,其中,123例肝功能异常癫痫患者血样为试验组,205例肝功能正常癫痫患者血样为对照组,采用LC-MS/MS方法测定两组血样(丙戊酸钠及代谢产物)的血药浓度,通过ROC曲线分析丙戊酸及其代谢产物浓度对肝功能异常的诊断价值。结果肝功能异常组患者丙戊酸钠及其3个代谢产物平均血药浓度均高于对照组,差异有统计学意义(P<0.05)。丙戊酸钠及其代谢产物的血药浓度均可作为诊断肝损伤的参考指标,5-羟基丙戊酸比丙戊酸钠有更好的诊断价值。结论丙戊酸钠代谢产物与肝毒性有关,能够作为肝损伤的诊断指标,可将其应用于临床,为丙戊酸钠有效给药提供参考。

Objective To analyze the correlation of valproic acid and its metabolites(2-propyl-4-pentenoic acid,3-hydroxy valproic acid,5-hydroxy valproic acid)with liver injury reference index.Methods 328 plasma samples from epilepsy patients were collected and divided into two groups(123 samples from patients with abnormal liver function,experimental group;205 samples from patients with normal liver function,control group).The plasma concentrations of valproic acid and its metabolites in the two groups were determined by LC-MS/MS method and the diagnostic value of the concentrations to liver disfunction was analyzed by ROC curve.Results The mean plasma concentration of valproic acid and its three metabolites in the patients with abnormal liver function was higher than that in the control group with was statistically difference(P<0.05).The concentration of valproic acid and its metabolites could be used as a reference for the diagnosis of liver injury,5-hydroxy valproic acid had better diagnostic value than valproic acid.Conclusion The metabolites of valproic acid were associated with hepatotoxicity,which could be used as a diagnostic index of liver injury and could be a reference for clinical safe application of valproic acid.