Cocktail Approach for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spot
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer
研究概览
简要总结
Phenotyping is an approach largely used for the evaluation of the activity of cytochromes and transporters in vivo. It consists of the administration of probe substances metabolised by a specific cytochrome or transported by P-glycoprotein (P-gp) for example, followed by the determination of a metabolic ratio or the evaluation of the plasmatic or urinary concentrations of the probe substances. The administration of a cocktail containing several probe substances allows the simultaneous evaluation of the activity of several cytochromes and P-gp in a single test.
The aim of this project is the validation of a phenotyping cocktail of low dose probe drugs for the assessment of cytochrome P450 and P-gp activities by simple capillary blood sampling and dried blood spot (DBS) analysis. The cocktail consists of caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, midazolam and fexofenadine for the simultaneous phenotyping of CYP1A2, CYP2B6, CYP2C9, CAP2C19, CYP2D6, CYP3A4 and P-gp, respectively.
The modulation of the activity of cytochromes or P-gp will be evaluated by the administration of inhibitors (fluvoxamine, voriconazole, quinidine) or inducer (rifampicin) of the metabolic pathways or the P-gp mediated transport.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male volunteers aged from 18 to 60 years
- •BMI between 18 and 25
- •Understanding of French language and able to give a written inform consent.
排除标准
- •Taking drugs which alter CYPs activity
- •Renal or hepatic impairment
- •Medical history of porphyria
- •Medical history of chronic alcoholism or abuse of psychoactive drugs
- •Liver transplantation
- •Sensitivity to any of the drugs used
- •Wearing contact lenses (risk of coloration with rifampicin)
- •ECG showing long QT interval (>0.46sec)
- •Alteration of hepatic tests
- •Presenting genetic polymorphism of poor CYP 2B6, 2C9, 2C19, 2D6 metabolisers
研究组 & 干预措施
CYP1A2, 2B6, 2C9, 2C19, 3A4 inhibitors
Oral intake of fluvoxamine (50 mg per day during 2 days) and voriconazole (400 mg) before oral intake of the cocktail probe drugs
干预措施: Cocktail probe drugs (Drug)
CYP2D6 and P-gp inhibitor
Oral intake of quinidine (200 mg) before oral intake of the cocktail probe drugs
干预措施: Cocktail probe drugs (Drug)
Probe cocktail alone
Oral intake of the cocktail probe drugs :
- bupropion 25 mg
- flurbiprofen 25 mg
- omeprazole 5 mg
- dextromethorphan 5 mg
- midazolam 1 mg
- fexofenadine 25mg
- Caffeine (a cup of coffee)
干预措施: Cocktail probe drugs (Drug)
CYPs and P-gp inducer
Oral intake of rifampicin (600 mg per day during 7 days) before oral intake of the cocktail probe drugs
干预措施: Cocktail probe drugs (Drug)
结局指标
主要结局
Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer
时间窗: 4 singles days spaced out with one week wash-out periods
次要结局
- correlation between plasma or urine and capillary concentrations for each probe cocktail drug(4 singles days spaced out with one week wash-out periods)
- comparison. between genotype and phenotype for each enzyme(one day)
研究者
Jules Desmeules
Pr
University Hospital, Geneva