Huang Yue, Yang Jing-Fang, Qi Xiao-Lian, Wang Yu-Qin, Wang Wei-Zhi, Chen Biao
Department of Neurobiology, Xuanwu Hospital of Capital University of Medical Sciences, Beijing 100053, China.
Zhonghua Yi Xue Za Zhi. 2004 Oct 17;84(20):1686-9.
To investigate the relationship between the genetic polymorphism of cytochrome CYP2C19 and CYP2C9 and the serum concentration of phenytoin (PHT) in patients with epilepsy.
The peripheral blood samples of 200 patients with epilepsy aged 2 - 68, were collected to undergo PCR. Denaturing high performance liquid chromatography (DHPLC) was used to detect the PCR products so as to examined the 2 common CYP2C19 allele variants and one CYP2C9 allele. The patients were treated with PHT of the dosage of 1.00 - 18.02 mg/kg alone. After 5 half-life periods venous blood was collected before the administration. Fluorescence polarization immunoassay was used to measure the PHT serum concentration standardized by dosage and body weight.
The allele frequencies of CYP2C19 * 2, CYP2C19 * 3, and CYP2C9 * 3 were 31%, 8%, and 6% respectively. Thirty-two patients with CYP2C19 and/or CYP2C9 allele variants were classified into 3 groups: extensive metabolizer (EM, n = 11) homozygous for CYP2C19 * 1/* 1 combined with CYP2C9 * 1/* 1 alleles, intermediate metabolizer (IM, n = 14) heterozygous for CYP2C19 * 1/* 2 or CYP2C19 * 1/* 3 alleles, and poor metabolizer (PM, n = 7) with the genotype of CYP2C19 * 2/* 2 or CP2C19 * 2/* 3, or CYP2C19 * 1/* 2 combined with CYP2C9 * 1/* 3. The genotype distribution rates of EM, IM, and PM were 34%, 44%, and 22% respectively. The PHT serum concentration of the PM group was (4.0 +/- 0.9) Css, significantly higher than that of the IM group [(3.0 +/- 0.9) Css, P < 0.05] and that of the EM group [(2.6 +/- 0.8) Css, P < 0.01] without a significant difference between the IM group and EM group.
Phenytoin is metabolized via CYP2C19 and CYP2C9. The PHT serum concentration of the PM is significantly higher. Genotyping helps predict the clinical response to PHT administration.
探讨癫痫患者细胞色素CYP2C19和CYP2C9基因多态性与苯妥英钠（PHT）血药浓度的关系。
收集200例年龄在2 - 68岁的癫痫患者外周血样本进行PCR。采用变性高效液相色谱法（DHPLC）检测PCR产物，以检测2种常见的CYP2C19等位基因变异和1种CYP2C9等位基因。患者单独接受剂量为1.00 - 18.02 mg/kg的PHT治疗。给药前经过5个半衰期后采集静脉血。采用荧光偏振免疫分析法测量经剂量和体重标准化后的PHT血药浓度。
CYP2C19 * 2、CYP2C19 * 3和CYP2C9 * 3的等位基因频率分别为31%、8%和6%。32例具有CYP2C19和/或CYP2C9等位基因变异的患者被分为3组：CYP2C19 * 1/* 1与CYP2C9 * 1/* 1等位基因纯合的广泛代谢型（EM，n = 11），CYP2C19 * 1/* 2或CYP2C19 * 1/* 3等位基因杂合的中间代谢型（IM，n = 14），以及基因型为CYP2C19 * 2/* 2或CP2C19 * 2/* 3或CYP2C19 * 1/* 2与CYP2C9 * 1/* 3组合的慢代谢型（PM，n = 7）。EM、IM和PM的基因型分布率分别为34%、44%和22%。PM组的PHT血药浓度为（4.0±0.9）Css，显著高于IM组[（3.0±0.9）Css，P < 0.05]和EM组[（2.6±0.8）Css，P < 0.01]，而IM组和EM组之间无显著差异。
苯妥英钠经CYP2C19和CYP2C9代谢。PM组的PHT血药浓度显著更高。基因分型有助于预测PHT给药的临床反应。
