| 范洁,詹三华,袁孔现.经皮冠状动脉介入术术后病人 CYP2C19*2、CYP2C19*3和 PON1基因多态性与氯吡格雷血药浓度及疗效的相关性分析[J].安徽医药,2020,24(2):385-389. |
| 经皮冠状动脉介入术术后病人 CYP2C19*2、CYP2C19*3和 PON1基因多态性与氯吡格雷血药浓度及疗效的相关性分析 |
| Genetic polymorphisms of CYP2C19*2、CYP2C19*3 and PON1 on blood concentration and effect of clopidogrel after percutaneous coronary intervention |
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| DOI：10.3969/j.issn.1009?6469.2020.02.045 |
| 中文关键词: 细胞色素 P450酶系统 对氧磷 氯吡格雷 血药浓度 色谱法，反相 发光测定法 多态现象，遗传 个体化医学 |
| 英文关键词: Cytochrome P?450 enzyme system Paraoxon Clopidogrel Plasma concentration Chromatography,reverse? phase Luminescent measurements Polymorphism,genetic Individualized medicine |
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| 中文摘要: |
| 目的探讨经皮冠状动脉介入术( PCI)术后病人 CYP2C19*2、CYP2C19*3及 PON1基因多态性与氯吡格雷血药浓度及疗效的相关性。方法采用定时定量焦磷酸测序技术检测 CYP2C19*2、CYP2C19*3及 PON1基因型。使用反相高效液相色谱法(RP?HPLC)法，以艾司唑仑为内标，测定氯吡格雷、羧酸氯吡格雷( SR26334)血药浓度。结果共纳入 51例 PCI术后病人，果显示 CYP2C19快代谢型血药浓度( 1.09±0.61)μg/mL与慢代谢型 SR26334血药浓度( 1.54±0.48)μg/mL之间差异有统计学意结义( P＝0.038 9)PON1(126C>G)野生型( CC型)病人 SR26334血药浓度( 1.45±0.63)μg/mL与突变型( CG+GG型)病人 SR26334血药浓度( 1.09±0.3，2)μg/mL差异有统计学意义( P＝0.0408)。 SR26334峰浓度与终点事件相关性分析中可见，正常组病人血药浓度( 1.51±0.48)μg/mL VS心血管事件组病人血药浓度( 1.06±0.65)μg/mL差异有统计学意义( P＝0.0481)CYP2C19基因型与终点事件的发生无明显相关。结论基因检测和血药浓度检测可为 ACS病人 PCI术后个体化抗血小板治疗，方案的制订提供依据，可作为临床药师开展药学服务的切入点之一。 |
| 英文摘要: |
| Objective To investigate the correlation between CYP2C19 and PON1 genetic polymorphisms and the blood concentra?tion of clopidogrel as well as its effect after percutaneous coronary intervention(PCI).Methods Genetic types of CYP2C19*2， CYP2C19*3，and PON1 were determined by real?time quantitative pyrosequencing.The concentrations of clopidogrel and clopidogrelcarboxylic acid(SR26334)were determined by reversed?phase high?performance liquid chromatography(RP?HPLC)using estazol? am as inner standard.Results Totally，this study enrolled 51 patients after PCI.Significant difference(P＝0.0389)was observed in the concentrations of SR26334 between CYP2C19 with fast and slow metabolic rates(1.09±0.61).The peak blood concentrations of SR26334 show significant difference(P＝0.0408)between the wild(CC)and mutated(CG+GG)PON1(126C>G).The peakconcentration of SR26334 and cardiovascular events show significant difference.There was no correlation between the genotyping ofCYP2C19 and end?point events.Conclusion Genotyping and blood concentration test provide a reference for the development ofindividualized antiplatelet therapy in patients with ACS after PCI，and can be a breakthrough for clinical pharmacists to carry out pharmaceutical services. |
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