【摘要】 目的:研究中国汉族健康男性志愿者CYP2C19遗传多态性对西酞普兰体内代谢的影响。方法:23名健康志愿者单次口服西酞普兰20 mg,服药前即刻抽取静脉血,用EDTA抗凝,提取基因组DNA,采用PCR-测序法测定其基因型。分别在服药前和服药后一定时间点取静脉血各5 mL,离心取血浆,用高效液相色谱-荧光检测法测定被试血浆西酞普兰药物浓度。用3P97分析软件分析药动学参数,并比较不同基因型受试者西酞普兰药动学的差异。结果:3名(3／23)受试者为CYF2C19慢代谢者(PMs),CYP2C19的多态性对药物代谢有影响,PMs的Cmax和AUC明显高于CYP2C19快代谢者。结论:CYP2C19慢代谢者在中国人群中比例较高,慢代谢者药物剂量应适当减低。更多还原

【Abstract】 Objective:To investigate the effects of cytochrome P450 2C19 gene polymorphism on the pharmacokinetics of citalopram in male Chinese. Methods:23 healthy Chinese volunteers were orally administered with a single dose of citalopram 20 mg. The blood samples from the volunteers were collected before and after the administration of citalopram and to isolate and measure the genotype CYP2C19 (wt, m1 and m2) of the volunteers by PCR-based sequencing. The measurements were performed by high-performance liquid chromatograph (HPLC) with fluorescent-detection and the pharmacokinetics parameters were analyzed with 3P97 software. Results:3 out of the 23 volunteers with poor metabolizing genotype (PM, genotypes of m1/m1 ,m2/m2 and m1/m2) showed significantly higher plasma concentration (Cmax) and the area under the plasma concentration versus time curve (AUC) of citalopram than the volunteers with extensive metabolizing genotype, suggesting that the polymorphism of CYP2C19 affected the pharmacokinetics of citalopram. Conclusion; The genetic polymorphism CYP2C19 makes an important contribution to the pharmaeokinetics of citalopram.更多还原