Xploring Venlafaxine Pharmacokinetic Variability by a Phenotyping Approach
试验速览
- 阶段
- 不适用
- 入组人数
- 205
- 试验地点
- 2
- 主要终点
- The CYP2C19 activity
研究概览
简要总结
Regarding the direct costs and the social value of depression, the decision of an antidepressant treatment prescription must be optimized as much as possible. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence burden and costs of affective disorders.
There is hope that biomarkers will be found to guide treatment selection. It might be of decisive interest to be able to assess an individual's metabolism activity. We propose here to explore the relationship between the activity of drug-metabolizing enzymes (DME) and transporters- assessed by a phenotypic approach and the efficacy of antidepressants. We will focus on venlafaxine (V) that provides a reasonable second-step choice for patients with depression and is used extensively in psychiatric practice, and the metabolism of which involves several cytochromes (CYP) P450 enzymes and the transporter P-gp.
Thus, the primary objective of this study is to study the correlation between the concentration of V and its metabolite ODesmethylV (V+ODV) and drug metabolism variability assessed by a phenotypic approach, in patients with major depressive disorder and MADRS ≥ 20 despite 4 weeks of V at 150mg or less
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient (Hospitalized or outpatient) with major depressive disorder and MADRS ≥ 20 at visit of selection
- •Patients non responders to V after 4 weeks of V at 150mg or less
- •Decision of the psychiatrist to increase the dose of V at visit of selection
- •Understanding of French language and able to give a written inform consent.
- •Informed consent signed to participate to the study
- •Individuals covered by social security regimen
排除标准
- •Patients treated by more than one antidepressant
- •Patients currently treated with one of the drug substrate of the cocktail
- •Sensitivity or contra-indication to any of the substrate drugs used
- •Current pregnancy, desire to get pregnant, or breastfeeding
- •Bipolar disorder and schizophrenia
研究组 & 干预措施
cocktail probe drugs
- A capsule of omeprazole ABBOTT® 10mg
- 10 mg of an oral liquid formulation of Dextrométhorphane bromhydrate (Drill Pierre FABRE MEDICAMENT® 5mg/5mL, syrup)
- 1 mg of an injectable solution of Midazolam for oral administration (Midazolam Panpharma® 1mg/mL, injectable solution)
- A tablet of fexofenadine Zentiva® 120mg
干预措施: cocktail probe drugs (Drug)
结局指标
主要结局
The CYP2C19 activity
时间窗: 2 hours
5-hydroxyomeprazole/omeprazole
The CYP2D6 activity
时间窗: 2 hours
dextrorphan/dextromethorphan ratio
The CYP3A4 activity
时间窗: 2 hours
1-hydroxymidazolam/ midazolam ratio
The P-gp activity
时间窗: 2, 3 and 6 hours
Fexofenadine AUC based on fexofenadine concentrations
次要结局
- Mood disorder(20, 40, 70 days)
- PRISE-M score(20, 40, 70 days)
- FISBER score(20, 40, 70 days)
- Tobacco use(20, 40, 70 days)
- MARS Score(20, 40, 70 days)
- Criteria for rating medication trials for antidepressant failure and level of resistance(20, 40, 70 days)
- QIDS-SR16(20, 40, 70 days)
- Anxiety scale Tyrer(20, 40, 70 days)