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目的探讨在合用丙戊酸(VPA)的儿童癫痫患者中,年龄、性别、体重、UGT1A4 142T>G基因多态性等影响因素对拉莫三嗪(LTG)疗效的影响,并明确中国南方癫痫儿童患者LTG的有效血药浓度。方法选取2010年1月至2016年9月在广州市妇女儿童医疗中心神经内科就诊的癫痫患儿72例,均采用LTG+VPA联合治疗。采用液质联用法检测LTG的浓度,采用限制性片段长度多态性聚合酶链式反应法测定UGT1A4 142T>G的基因型。采用卡方检验、非参数检验、Logistic回归分析等探讨各影响因素与LTG疗效的相关性及有效血药浓度。结果合用VPA时,年龄越小、体重越轻,其疗效相对差。男性较女性容易获得较好疗效。UGT1A4 142T>G对LTG疗效无显著影响。合用VPA时,患儿LTG的有效血药浓度为>2μg/m L。结论年龄显著影响LTG的疗效;合用VPA时,南方癫痫患儿LTG的有效血药浓度应>2μg/m L;本研究能为中国南方癫痫儿童的个体化给药提供参考。
Objective To investigate the effects of age, gender, body weight, UGT1A4 142T> G polymorphism on the efficacy of lamotrigine (LTG) in children with epilepsy combined with valproic acid (VPA) Effective plasma concentrations of LTG in children. Methods Seventy-two children with epilepsy were enrolled in the Department of Neurology, Guangzhou Women and Children Medical Center from January 2010 to September 2016. All the patients were treated with combination of LTG and VPA. The concentration of LTG was detected by LC-MS, and the genotype of UGT1A4 142T> G was determined by restriction fragment length polymorphism polymerase chain reaction. Using chi-square test, nonparametric test, logistic regression analysis and other factors to explore the correlation between LTG efficacy and effective plasma concentration. Results VPA combined, the younger, the lighter the body weight, the effect is relatively poor. Men are more likely to get better results than women. UGT1A4 142T> G had no significant effect on LTG efficacy. With VPA, the effective plasma concentration of LTG in children is> 2 μg / m L. Conclusions Age significantly affects the efficacy of LTG. When combined with VPA, the effective plasma concentration of LTG in the children with epilepsy in the south should be> 2μg / m L; this study can provide reference for the individualized administration of epilepsy children in southern China.