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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 analyze the main factors influencing the plasma concentrations of clopidogrel active metabolites in patients with acute coronary syndrome (ACS). Methods A total of 105 patients with ACS were given aspirin 100 mg · d -1 and clopidogrel 75 mg · d -1 for 4 d after oral administration. On the fifth day, Blood 4 m L, with EDTA anticoagulation. 20 ml of 500 ml·L -1 2-bromo-3’-methoxyacetophenone (MPB) solution was immediately added to detect the concentration of clopidogrel active metabolites. The other 2 m L for fluorescence detection of cytochrome P450 2C19 * 2 (CYP2C19 * 2), * 3 and Pn1 genotypes. Univariate analysis was used to explore the effect of dichotomous variables and grade data on the plasma concentrations of active metabolites of clopidogrel. The Spearman analysis was used to explore the correlation between the plasma concentrations of active metabolites of clopidogrel and the continuous variables. Results Diabetes mellitus, hyperlipidemia and PON1 were carried. The plasma concentrations of active metabolites of clopidogrel were negatively correlated (P <0.05) after percutaneous coronary intervention, β-blockers, statins, serum Albumin (ALB) was positively correlated with the concentration of active metabolite of clopidogrel (P <0.05). Conclusions Diabetes mellitus, hyperlipidemia, PON1 transport and percutaneous coronary intervention may decrease plasma concentration of active metabolites of clopidogrel. However, ALB and combined beta-blockers or statins may increase their blood levels Drug concentration.