吴斯,谢娟,李龙宽
WU Si,XIE Juan,LI Longkuan

• 1:贵州医科大学附属人民医院
• 2:贵州医科大学第三附属医院

摘要(Abstract)：

目的:研究癫痫儿童血液中丙戊酸毒性代谢产物2-丙基-4-戊烯酸(4-ene-VPA)血药浓度与谷丙转氨酶(ALT)的关系。方法:选取96例癫痫儿童作为研究对象,采用反向高效液相色谱法(RP-HLPC)法测定患儿血浆中4-ene-VPA的血药浓度,采用常规生化检测法检测患儿静脉血中ALT的含量,并进行相关性分析。结果:0~≤2岁组癫痫患儿血浆中4-ene-VPA血药浓度与ALT正相关(P=0.018,r=0.621)关系。结论:对于0~≤2岁癫痫患儿,服用丙戊酸时应重点监测肝功能。
Objective: To explore the correlation between plasma concentration of sodium valproate's metabolites 2-propyl-4-pentenoic and ALT. Methods: A total of 96 cases of epileptic children patients who took sodium valproate medicine over 7 days and reached steady drug concentration in plasma were enrolled in this study. RP-HLPC was adopted to determine the blood concentration of 2-propyl-4-pentenoic. The ALT content in venous blood of patients was determined by conventional biochemical detection method. The correlation analysis between the blood concentration of 2-propyl-4-pentenoic and ALT content in venous blood was conducted by SPSS19. 0. Results: The blood concentration of 2-propyl-4-pentenoic was positively correlated to ALT content in venous blood in 0 ~ ≤2 years old patients( P =0. 018,r = 0. 621),but there was no significant correlation between the level of 4-ene-VPA and ALT in other age group. Conclusion: For 0 ~ ≤2 years old epileptic children patients who took sodium valproate,liver function should be monitored emphatically.

关键词(KeyWords)： 丙戊酸;2-丙基-4-戊烯酸;反向高效液相色谱法;丙戊酸的代谢产物;血药浓度
valprioc acid;2-propyl-4-pentenoic;reverse high-performance liquid chromatography;valproate's metabolites;plasma concentration

Abstract:

Keywords:

基金项目(Foundation): 贵州省卫生厅基金(项目编号:gzwkj2010-1-003)

作者(Author): 吴斯,谢娟,李龙宽
WU Si,XIE Juan,LI Longkuan

DOI: 10.19367/j.cnki.1000-2707.2015.10.012

参考文献(References)：

• [1]姜玉武,谢涵.特发性全面性癫痫的遗传学研究进展[J].北京大学学报:医学版,2013(2):186-191.
• [2]黄成坷,王增寿,周伶俐.丙戊酸钠血药浓度监测治疗儿童癫痫的临床意义[J].中国医院药学杂志,2012(9):710-712.
• [3]Glauser T,Ben-Menachem E,Bourgeois B,et al..Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes[J].Epilepsia,2013(2):551-563.
• [4]Kiang TK,Teng XW,Karagiozov S.Role of oxidative metabolism in the effect of valpoic Acid on markers of cell viability,necrosis,and oxidativestress in sandwich-cultured rat h-Epatocytes[J].Toxicol Sci,2010(2):501-509.
• [5]Argikar UA,Remmel RP.Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4,UGT1A8,and UGT1A10[J].Drug Metab Dispos,2009(1):229-236.
• [6]Tan L,Yu JT,Sun YP,et al.The influence of cytochrome oxidase CYP2A6,CYP2B6,and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic pati-ents[J].Clin Neurol Neurosurg,2010(4):320-323.
• [7]Ghodke-Puranik Y,Thorn CF,Lamb JK,et al.Valproic acid pathway:pharmacokinetics and pharmacodynamics[J].Pharmacogenet Genomics,2013(4):236-241.
• [8]Kiang TK,Teng XW,Surendradoss J,et al.Glutathione depletion by valproic acid in sandwich-cultured rat hepatocytes:Role of biotransformation and temporal relationship with onset of toxicity[J].Toxicol Appl Pharmacol,2011(3):318-324.
• [9]Amini-Shirazi N,Ahmadkhaniha R,Shadnia S,et al.Determination of VPA and its Two Important Metabolites in Iranian Overdosed Patients[J].International Journal of Pharm acology,2010(6):854-862.
• [10]储小曼,郭岑,张丽芳.丙戊酸的代谢特征与其肝毒性的相关性[J].中国医院药学杂志,2013(19):1611-1614.
• [11]Lee MS,Lee YJ,Kim BJ,er al.The Relationship between Glucuronide Conjugate levels and Hepatotoxicity after Oral Administration of Valproic Acid[J].Arch Pharm Res,2009(7):1029-1035.

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