中国临床药理学杂志2017,Vol.33Issue(7):595-598,4.DOI:10.13699/j.cnki.1001-6821.2017.07.006
癫痫患者细胞色素P450 2C19 * 2基因型与奥卡西平活性代谢物浓度相关性研究
Relationship between cytochromes P450 2C19 * 2 genotype and the concentration of the active oxcarbazepine metabolite in pediatric patients with epilepsy
摘要
Abstract
Objective To evaluate the correlation between cytochromes P450 2C19 * 2 (CYP2C19 * 2) genotype and the concentration of the active oxcarbazepine metabolite in patients with epilepsy.Methods We included 65 patients with epilepsy that used oxcarbazepine for treatment who were under 16 years old.Then collecte blood,after steady state(after the 7th dose) and use reversed-phase high-performance liquid chromatography (RP-HPLC) to determine the trough concentration of monohydroxycarbazepine (MHD) which is an active oxcarbazepine metabolite.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis were used to determine CYP2C19 * 2 genotype.The differences between the groups were tested by using single factor analysis of variance;Multi factors analysis was tested by using multiple linear regression model and gender,age,daily dosage,dosage by weight and genotype were considered as parameters.Results Of 65 patients with epilepsy,35 were homozygous wild-type (* 1/* 1) with an average MHD concentration (17.41 ±7.58) μg · mL-1;22 were heterozygote(* 1/* 2) with an average MHD concentration (21.68 ±7.69)μg · mL-1;8 were homozygous mutation(* 2/* 2) with an average MHD concentration (19.38 ± 9.74) pg · mL-1.The differences of plasma concentration of MHD between three genotypes are not statistically significant (P > 0.05);In multiple linear regression model,the daily dose was positively related to MHD concentration (P < 0.05),and others are not.Conclusion There is no significant difference between CYP2C19 * 2 genotype and the concentration of MHD in patients with epilepsy.For pediatric patients treated with oxcarbazepine,therapeutic drug monitoring is more recommended than genetic testing.关键词
奥卡西平/癫痫/儿童/基因型/血药浓度Key words
oxcarbazepine/epilepsy/children/genotype/plasma concentration分类
医药卫生引用本文复制引用
周鑫,马凌悦,向倩,胡琨,李敏,吴晔,周颖,崔一民..癫痫患者细胞色素P450 2C19 * 2基因型与奥卡西平活性代谢物浓度相关性研究[J].中国临床药理学杂志,2017,33(7):595-598,4.基金项目
首都临床特色应用研究基金资助项目(Z151100004015044) (Z151100004015044)