阿托伐他汀与氯吡格雷对ACS患者氯吡格雷羧酸衍生物血浓度与血小板聚集率的影响

Effects of atorvastatin and clopidogrel on clopidogrel carboxylic acid derivatives blood concentration and platelet aggregation rate in patients with acute coronary syndrome

目的:测定急性冠状动脉综合征(ACS)患者氯吡格雷羧酸衍生物血浓度和血小板聚集率,观察阿托伐他汀和氯吡格雷有无相互作用。方法:对照组为25例健康受试者,ACS组为66例ACS患者。均口服阿司匹林100mg/d、氯吡格雷75mg/d、阿托伐他汀20mg/d,5d后暂停阿托伐他汀,继续氯吡格雷和阿司匹林口服4d,分别于第5天、第9天采用液相色谱串联质谱法测量氯吡格雷羧酸衍生物血浓度,流式细胞仪测定血小板聚集率,比较两组差异。结果:对照组第5天和第9天氯吡格雷羧酸衍生物血浓度分别为(5.76±0.87)ng/dl和(5.67±0.88)ng/dl(P=0.351),血小板聚集率分别为(44.25±16.37)%与(47.61±16.67)%(P=0.083)。ACS组第5天和第9天氯吡格雷羧酸衍生物血浓度分别为(5.96±0.87)ng/dl和(5.86±0.97)ng/dl(P=0.115),血小板聚集率分别为(47.70±15.07)%与(47.02±15.45)%(P=0.622)。相关性分析显示,血氯吡格雷羧酸衍生物浓度和血小板聚集率呈正相关。结论:氯吡格雷羧酸衍生物血浓度和血小板聚集率相关性良好,氯吡格雷和阿托伐他汀未见相互作用。

Objective：To investigate the effects of atorvastatin and clopidogrel on carboxylic acid derivatives blood concentration and rate of platelet aggregation in patients with acute coronary syndrome（ACS）.Method：The control group included 25healthy subjects,ACS group included 66ACS patients.All subjects took aspirin 100 mg/d,clopidogrel 75mg/d,and atorvastatin 20mg/d.Five days later,atorvastatin was stopped,while clopidogrel and aspirin orally continued four days.At fifth day and ninth day,we measured clopidogrel carboxylic acid derivatives blood concentration by high performance liquid chromatography coupled with tandem mass spectrometry（HPLC-MS/MS）,and tested platele aggregation rate by flow cytometry.Result：At fifth and ninth day,clopidogrel carboxylic acid derivatives blood concentrations were（5.76±0.87）ng/dl and（5.67±0.88）ng/dl（P= 0.351）,platelet aggregation rates were（44.25±16.37）% and（47.61±16.67）%（P=0.083）respectively in control group;while（5.96±0.87）ng/dl and（5.86±0.97）ng/dl（P=0.115）,（47.70±15.07）%and（47.02± 15.45）%respectively in ACS group（P=0.622）.Correlation analysis showed that the derivative concentration of blood clopidogrel carboxylic acid and platelet aggregation rate had positive correlation.Conclusion：Blood levels of clopidogrel carboxylic acid derivative and platelet aggregation have strong and positive correlation.There is no interaction between atorvastatin and clopidogrel.