CYP2C19基因多态性对艾司西酞普兰血药浓度的影响

Effects of CYP2C19 Gene Polymorphism on Blood Concentration of Escitalopram

目的:研究细胞色素P4502C19(CYP2C19)基因多态性对艾司西酞普兰(Es)血药浓度的影响。方法:采用HPLC法建立Es血药浓度检测方法并计算标准血药浓度。随机选择70例抑郁症患者为研究对象,单独使用Es对70例抑郁症患者治疗两周后,检测其血药浓度并计算标准血药浓度、采集汉密尔顿抑郁量表(HAMD)和药物副反应量表(TESS)分析携带不同基因类型的抑郁症患者对Es的代谢类型。结果:成功建立了Es的HPLC检测方法,最低检测浓度为10 ng·ml-1,最低检测限量为3.6 ng。依据基因类型的不同,将70例抑郁症患者分成A、B、C三组,组间标准血药浓度差异有统计学意义(P<0.01)。野生型、杂合突变体及纯合突变体的代谢类型分别是EM、IM和PM,各组间标准血药浓度,汉密尔顿抑郁量表(HAMD)和药物副反应量表(TESS)分析结果差异均有统计学意义(P<0.05)。结论:CYP2C19基因型不同的抑郁症患者对Es的代谢水平、治疗效果及不良反应情况不相同,临床应根据患者的基因类型,制定个体化的给药方案。

Objective： To study the effects of CYP2C19 gene polymorphism on blood concentration of escitalopram （Es）. Meth- ods： The blood concentration of Es was detected by HPLC and the standard blood concentration was calculated. Totally 70 patients with dysthymia disorders were selected and treated with Es for 2 weeks. DNA was extracted from the peripheral blood and amplified by PCR. The PCR products were digested by restriction endonuclease （HphI） and the genotype of CYP2C19 was determined by eleetre- phoresis. The therapeutic and adverse effects of Es in the 70 patients were evaluated by HAMD analysis and TESS. Results： The HPLC determination method for Es was established successfully with the minimum detection concentration of 10 ng · m1-1 and minimum detection limit of 3.6ng. According to the genotype of CYP2C19, the patients were divided into three groups, wild type group, hetero- zygous mutant group and homozygous mutant group, and the standard blood concentration among them had significant difference （P 〈 0.01 ）. TESS and HAMD of the three groups also had significant differences （P 〈 0.05）. The metabolism type of the three groups was EM, IM and PM, respectively. Conclusion： The metabolism, efficacy and adverse effects of Es are controlled by different genotypes of CYP2C19, therefore, individualized medication should be carried out according to the genotypes of patients.