NCT01258504已完成不适用
Influence of Cytochrome P450 3A4 (CYP3A4)-Induction by St. John's Wort (SJW) on the Steady State Pharmacokinetics of Bosentan
Gerd Mikus1 个研究点 分布在 1 个国家目标入组 13 人开始时间: 2011年1月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Cmax of Bosentan
研究概览
简要总结
The aim of the present study is to assess the impact of the cytochrome P450 2C9 (CYP2C9) genotype (*2 and *3 allele versus wild type; ~3-5% poor metabolisers in Caucasian population) on the pharmacokinetics of bosentan and the impact of CYP3A4-induction by St. John's wort (SJW) on steady state bosentan which is a CYP3A4 inducer itself.
详细描述
We evaluate the effect of SJW on bosentan pharmacokinetics and its relationship to polymorphisms in the CYP2C9 gene known to reduce CYP2C9 activity. This study will be conducted at bosentan steady-state because concentrations decrease in the first 10 days of treatment due to auto-induction of the metabolism.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Good state of health (physically and mentally)
- •Able to communicate well with the investigator, to understand and comply with the requirements of the study
- •Voluntarily signed informed consent after full explanation of the study to the participant.
- •No clinically relevant findings in any of the investigations of the pre-study examination, especially aminotransferase elevations ≥ 3 × upper limit of normal(ULN). Minor deviations of other laboratory values from normal range may be acceptable, if judged by the investigator to be of no clinical relevance.
- •Known genotype for CYP2C9 polymorphism.
- •Agreement to abstain from alcoholic beverages during the time of the study.
- •Females must agree to use a reliable contraception (Pearl Index <1%), e.g. double barrier method.
排除标准
- •Any regular drug treatment within the last two months, except for oral contraceptives in female volunteers and L-thyroxine.
- •Any intake of a substance known to induce or inhibit drug metabolising enzymes or drug transporters within a period of less than 10 times the respective elimination half-life or 2 weeks, whatever is longer
- •Any participation in a clinical trial within the last month before inclusion
- •Any physical disorder which could interfere with the participant's safety during the clinical trial or with the study objectives
- •Any acute or chronic illness, or clinically relevant findings in the pre-study examination, especially: a) any condition, which could modify absorption, distribution, metabolism, or excretion of the drug regimen under investigation b) Allergies (except for mild forms of hay fever) or history of hypersensitivity reactions
- •Regular smoking
- •Blood donation within 6 weeks before first study day
- •Excessive alcohol drinking (more than approximately 20 g alcohol per day)
- •Inability to communicate well with the investigator due to language problems or poor mental development
- •Inability or unwillingness to give written informed consent
- •Known or planned pregnancy or breast feeding
- •Pre-existing moderate or severe liver impairment
研究组 & 干预措施
CYP2C9 wild type
CYP2C9 wild type ="extensive metaboliser"
- Administration of bosentan: 1 x 125 mg p.o. on days 1 and 20, 2 x 62.5 mg p.o. on day 2, 2 x 125 mg p.o. on days 3-19
- Administration of St. Johns Wort: 3 x 300 mg daily p.o. on days 11-19 and 2 x 300 mg on day 20
干预措施: St. Johns Wort (Drug)
CYP2C9 mutant
CYP2C9 *2/*2 or 2*/*3 or *3/*3 = "poor metaboliser"
- Administration of bosentan: 1 x 125 mg p.o. on days 1 and 20, 2 x 62.5 mg p.o. on day 2, 2 x 125 mg p.o. on days 3-19
- Administration of St. Johns Wort: 3 x 300 mg daily p.o. on days 11-19 and 2 x 300 mg on day 20
干预措施: St. Johns Wort (Drug)
结局指标
主要结局
Cmax of Bosentan
时间窗: after first dose, at steady-state and during SJW
AUC of Bosentan
时间窗: 0-infinity; during dosing interval
次要结局
未报告次要终点
研究者
Gerd Mikus
Head of Clinical Research Unit
Heidelberg University
研究点 (1)
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