Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Platelet aggregation inhibition measured by optical aggregometry in presence of adenosine diphosphate (ADP) 20 μmol/L and 5 μmol/L.
研究概览
简要总结
Clopidogrel is a platelet aggregation inhibitor witch prevents thrombotic events in patients with atherosclerotic vascular disease. To date, 4 to 30 % of patients are considered as poor, low or non-responder to this therapeutic. However, drug-drug interactions may lead to decrease the clopidogrel responsiveness. Many arguments are in support to a drug-drug interaction between clopidogrel and fluoxetine (selective serotonin reuptake inhibitor). On the pharmacokinetic level, fluoxetine inhibits the cytochroms involved in the production of clopidogrel active metabolite. On the pharmacodynamic level fluoxetine could increase the risk of hemorrhage by inhibiting the serotonin platelet reuptake and thus enhance the antiplatelet effect of clopidogrel.
The purpose of this study is to investigate the influence of fluoxetine on pharmacokinetic and pharmacodynamic of clopidogrel.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Signed an informed consent
- •Body mass: 60 to 85 Kg
- •Platelet count: 180 to 350 G/L
- •% platelet aggregation > 70%
- •Subjects are to be in good health as determined by a medical history, physical examination including vital signs, and clinical laboratory test results including liver function, renal and full blood count
排除标准
- •Subject with an history of seizure disorder
- •Subject with a known allergy fluoxetine or clopidogrel
- •Cigarette smoking
- •Subject with a history of hemorrhagic disease
- •Peptic ulcer
- •Psychiatric disorders
- •Participation in another clinical or device trial within the three previous months
- •Subject who is currently taking medications
- •Subject who is currently taking medications for depression
- •Subject with an history of depression (MADRS score < 15)
- •Hepatic insufficiency
研究组 & 干预措施
1
Clopidogrel then fluoxetine+clopidogrel
干预措施: Clopidogrel then fluoxetine+clopidogrel (Drug)
2
Fluoxetine+clopidogrel then clopidogrel
干预措施: Fluoxetine+clopidogrel then clopidogrel (Drug)
结局指标
主要结局
Platelet aggregation inhibition measured by optical aggregometry in presence of adenosine diphosphate (ADP) 20 μmol/L and 5 μmol/L.
时间窗: Before first fluoxetin taking, during clopidogrel taking
次要结局
- Level of phosphorylated VASP (vasodilator- stimulated phosphoprotein), a good index of P2Y12 activity (platelet receptor of clopidogrel) and P-selectin by flow cytometry.(Before first Fluoxetine taking and during Clopidogrel taking)
- Determination of clopidogrel and its metabolites in plasma by LC/MS-MS method(During clopidogrel taking)