TDM结合CYP2C19基因型指导癫痫患儿个体化服用苯妥英钠的临床效果

Clinical effects of individualized administration of phenytoin sodium in epileptic children guided by TDM combined with CYP2 C19 genotype

目的探讨治疗药物监测(TDM)结合CYP2C19基因型指导癫痫患儿个体化服用苯妥英钠的临床效果.方法采用聚合酶链反应-限制性片段长度多态性检测技术对2016年1月至2017年6月在郑州大学第二附属医院就诊的232例癫痫患儿的CYP2C19基因型进行检测,其中仅服用苯妥英钠进行抗癫痫治疗的患儿78例,将这78例患儿根据CYP2C19基因型分为快、中、慢代谢组,对每组患儿分别给予不同剂量的苯妥英钠,监测患儿体内苯妥英钠的血药浓度.结果232例患儿体内CYP2C19具有基因多态性,6种基因型*1/*1、*1/*2、*1/*3、*2/*2、*2/*3和*3/*3型的发生率分别为39.7%、41.8%、6.5%、9.5%、2.1%、0.4%;其中仅服用苯妥英钠进行抗癫痫治疗的78例患儿中快、中、慢代谢组稳态血药浓度比较差异未见统计学意义(P>0.05),不良反应发生率比较差异未见统计学意义(P>0.05).结论服用苯妥英钠进行抗癫痫治疗的患儿体内CYP2C19具有多态性,可以在患儿服用苯妥英钠时进行剂量调整,实现苯妥英钠应用的个体化.

Objective To investigate the clinical effects of therapeutic drug monitoring ( TDM) combined with CYP2 C19 genotype on individualized administration of phenytoin sodium in children with epilepsy. Methods Polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) was used to detect CYP2 C19 genotype in 232 children with epilepsy who were treated in the Second Affiliated Hospital of Zhengzhou University from January 2016 to June 2017. Among them, 78 children only took phenytoin sodium for antiepileptic treatment, and they were divided into fast, moderate and slow metablic groups by CYP2C19 genotypes. In fast, moderate and slow metabolic groups, different doses of phenytoin sodium were given to each group to monitor the blood concentration of phenytoin sodium in children. Results CYP2C19 gene polymorphism was found in 232 children. The incidences of six genotypes,*1 /* 1,* 1 /* 2,* 1 /* 3,* 2 /* 2,* 2 /* 3 /* 3 were 39. 7%, 41. 8%, 6. 5%, 9. 5%, 2. 1% and 0. 4% respectively. There was no difference in steady-state blood drug concentration among fast, moderate and slow metabolic groups in 78 children treated with phenytoin sodium only ( P>0. 05 ). There was no significant difference in the incidence of adverse reactions among the three groups ( P>0. 05 ). Conclusions CYP2 C19 has polymorphism in children who take phenytoin sodium for antiepileptic treatment. Clinicians can adjust the dosage of phenytoin sodium to realize the individualization of the application of phenytoin sodium.