Correlation Between Phenotypic Activity of CYP2C9 and Genetic Polymorphism in CYP2C9 and Warfarin Metabolism.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Formation clearance of CYP2C9 mediated warfarin metabolites
研究概览
简要总结
The anticoagulant effect of warfarin varies greatly among individuals. Some of this variability is attributed to differences in the activity of CYP2C9, the predominant enzyme involved in the metabolism of S-warfarin.
The present study is designed to define the differences in warfarin metabolism among healthy individuals carrying different CYP2C9 genotypes. In addition, the study will define the correlation between the phenytoin metabolic ratio, a marker of CYP2C9 activity in vivo, and warfarin metabolism.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age range of 20-50 years old
- •The absence of significant disease states
排除标准
- •Known hypersensitivity to warfarin or phenytoin
- •Known hepersensitivity to penicillins or cephalosporins (Dicloxacillin part)
- •The presence of significant disease states
- •Regular use of drugs (including birth control pills)
研究组 & 干预措施
CYP2C9 substrate: Warfarin, Phenytoin, Losartan, Flurbiprofen, Siponimod.
Each participant may be given at least one of the following CYP2C9 substrates: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.
干预措施: Warfarin (Drug)
CYP2C9 substrate: Warfarin, Phenytoin, Losartan, Flurbiprofen, Siponimod.
Each participant may be given at least one of the following CYP2C9 substrates: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.
干预措施: Phenytoin (Drug)
CYP2C9 substrate: Warfarin, Phenytoin, Losartan, Flurbiprofen, Siponimod.
Each participant may be given at least one of the following CYP2C9 substrates: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.
干预措施: Losartan & Hydrochlorothiazide (Drug)
CYP2C9 substrate: Warfarin, Phenytoin, Losartan, Flurbiprofen, Siponimod.
Each participant may be given at least one of the following CYP2C9 substrates: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.
干预措施: Flurbiprofen (Drug)
CYP2C9 substrate: Warfarin, Phenytoin, Losartan, Flurbiprofen, Siponimod.
Each participant may be given at least one of the following CYP2C9 substrates: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.
干预措施: Siponimod (Drug)
CYP2C9 substrate: Warfarin, Phenytoin, Losartan, Flurbiprofen, Siponimod.
Each participant may be given at least one of the following CYP2C9 substrates: Warfarin, Phenytoin, Losartan, Flurbiprofen and Siponimod.
干预措施: Dicloxacillin (Drug)
结局指标
主要结局
Formation clearance of CYP2C9 mediated warfarin metabolites
时间窗: 2 weeks
Warfarin oral clearance
时间窗: 2 weeks
Phenytoin Metabolic Ratio, oral clearance of Phenytoin, Formation clearance of p-HPPH.
时间窗: Up to 4 days (96 hours) post drug intake.
Following single dose administration of Phenytoin 300 mg, at least two blood samples 12 and 24 hours post drug intake will be obtained and urine will be collected for at least 24 hours.
Losartan oral clearance and the formation clearance of E3174.
时间窗: Up to 48 hours post drug intake.
For those participant who receive losartan, blood sample will be collected periodically over 48 hours and urine will be collected for 48 hours. Losartan oral clearance and the formation clearance of E3174 will serve as primary outcomes.
Flurbiprofen oral clearance.
时间窗: Up to 36 hours post drug intake.
Some participant will receive single dose of flurbiprofen 50 mg. Plasma samples will be obtained periodically over 24 hours and urine will be collected.
Siponimod oral clearance.
时间窗: Up to 2 weeks following drug intake.
Some participants will receive single dose of siponimod 0.25 mg and blood samples will be obtained periodically over the next 2 weeks. Pharmacodynamic response will be evaluated by repeated ECG records and measurement of CBC and potassium.
Change in S-warfarin and phenytoin pharmacokinetic parameters.
时间窗: Up to 6 weeks following the administration of the first warfarin single dose.
Some patients will receive phenytoin (300 mg) and at least one week later warfarin (20 mg) twice before and after intake of dicloxacillin 500 mg QID for 21 days.
Correlation between CYP2C9 substrate pharmacokinetics and genetic polymorphism.
时间窗: For up to 5 years following drug intake.
Using candidate gene approach, sequencing of relevant regions in chromosome 10 will be conducted. Potential genetic alterations (SNPs, deletions, insertions, p-VNTR) will be correlated with pharmacokinetic parameters of CYP2C9 substrates.
次要结局
未报告次要终点