分析急性冠状动脉综合征患者体内氯吡格雷活性代谢产物的影响因素

Analysis the factors of influencing on the concentrations of clopidogrel active metabolite in plasma of patients with acute coronary syndrome

目的分析影响急性冠状动脉综合征(ACS)患者体内氯吡格雷活性代谢产物血浆浓度的主要因素。方法105例ACS患者均给予阿司匹林100 mg·d^(-1)及氯吡格雷75 mg·d^(-1),连续口服4 d;第5天晨起空腹给药1 h后,抽取静脉血4 m L,用乙二胺四乙酸抗凝。其中2 m L立即加入500 mmol·L^(-1)的2-溴-3’-甲氧基苯乙酮(MPB)溶液20μL,用于检测氯吡格雷活性代谢产物的浓度;另2 m L用于荧光检测细胞色素P450 2C19*2(CYP2C19*2)、*3和氧磷酶1(PON1)基因型。用单因素分析探索二分类变量及等级资料对氯吡格雷活性代谢产物血药浓度的影响,用Spearman分析探索氯吡格雷活性代谢产物血药浓度与连续性变量的相关性。结果糖尿病、高脂血症、PON1携带、进行经皮冠状动脉介入手术后与氯吡格雷活性代谢产物血药浓度呈负相关(P<0.05),β受体阻滞药、他汀类药物、血清白蛋白(ALB)与氯吡格雷活性代谢产物的浓度呈正相关(P<0.05)。结论糖尿病、高脂血症、PON1携带及进行经皮冠状动脉介入手术后等可减少氯吡格雷活性代谢产物血药浓度,而ALB以及合用β受体阻滞药或他汀类药物可增加其血药浓度。

Objective To discuss the factors influencing the concentra- tions of clopidogrel active metabolite in plasma of patients with acute cor- onary syndrome （ACS）. Methods One hundred and five patients with ACS were administrated aspirin （100 mg·d^-1） and clopidogrel （75 mg·d^-1 ） for 4 days. On day 5 ,blood samples （ approximate 4 mL） were collected at 1 h after administration with empty stomach. Half of the blood added 20 μL 2 - Bromo - 3 ＇ - methoxyacetophenone （ MPB, 500 mmol·L^-1） immediately was used for the determination of elopidogrel active metabolite. And the other was used for detecting the cytochrome P450 2C19 ＊ 2 （ CYP2C19 ＊ 2）, ＊ 3, and paraoxonase - 1 （ PON1 ）. By using single factor analysis, the binary variable and ranked data related to the blood drug concentration of clopidogrel active metabolites were analyzed. And the measurement data related to the blood drug concentration of clopidogrel active metabolites were analyzed using Spearman analysis. Results The concentration of clopidogrel active metabolites had a significantly negative correlation with diabetes, hyperlipidemia, percutaneous coronary intervention （ PCI）, PON1 carrier（P 〈 0. 05 ） ; but positive correlation with β-blockers, statins and serum albumin （ALB） （P 〈 0. 05 ）. Conclusion The diabetes, hyperlipidemia, PCI can reduce the concentration of clopidogrel active metabolites in blood;while the ALB, -blockers and statins can increase the concentration of clopidogrel active metabolites in blood.