Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Primary Pharmacokinetic Measure: Area Under the Curve (AUC)
研究概览
简要总结
Purpose: Grapefruit juice is one of the most extensively studied dietary/natural substances shown to interact with a variety of medications. However, unanswered questions remain regarding the causative ingredients and mechanisms underlying such drug-grapefruit juice interactions. Compounds in grapefruit juice called furanocoumarins have been established as major causative ingredients, which act by inhibiting the elimination (metabolism) of drugs, leading to increased circulating drug concentrations. Increased drug concentrations can in turn lead to increased drug potency or even toxicity. Grapefruit juice also has been shown, paradoxically, to decrease circulating concentrations of some drugs, including the non-sedating antihistamine agent, fexofenadine (Allegra), which undergoes negligible metabolism. Whether or not furanocoumarins mediate the decrease in fexofenadine concentrations is unknown. The purpose of the proposed study is to compare the effects of a "furanocoumarin-free" grapefruit juice with grapefruit juice on circulating concentrations of fexofenadine.
详细描述
Participants: Healthy volunteers of any race/ethnicity, ranging in age from 18 to 65 years, will be enrolled.
Procedures (methods): Procedures will include administration of water, furanocoumarin-free grapefruit juice, or grapefruit juice with fexofenadine; placement of an intravenous (IV) line; and collection of blood over 72 hours.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
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
- •Men or women between the ages of 18 and 65
- •Normal screening laboratory test results
- •Able to understand the informed consent form
- •Willing to abstain from grapefruit products and all fruit juices for one week prior to and during the study
- •Willing to abstain from alcohol and caffeinated beverages the evening prior to each study day
排除标准
- •History of intolerance to grapefruit products
- •History of any allergy or hypersensitivity to grapefruit products or fexofenadine
- •History of significant medical conditions that the study physician believes would increase risk
- •History of significant alcohol abuse and/or illicit drug use
- •Tobacco use within the month preceding the study
- •Pregnancy or breast-feeding
- •Taking concomitant medications, both prescription and non-prescription (including herbal products), known to alter fexofenadine blood levels or P-gp and/or OATP activity (women stabilized on hormonal methods of birth control will be allowed to participate)
研究组 & 干预措施
Sequence 1: Water, GFJ, FC-free GFJ
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
干预措施: Fexofenadine (Drug)
Sequence 2: Water, FC-free GFJ, GFJ
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
干预措施: Fexofenadine (Drug)
Sequence 3: GFJ, FC-free GFJ, Water
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
干预措施: Fexofenadine (Drug)
Sequence 4: GFJ, Water, FC-free GFJ
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
干预措施: Fexofenadine (Drug)
Sequence 5: FC-free GFJ, GFJ, Water
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
干预措施: Fexofenadine (Drug)
Sequence 6: FC-free GFJ, Water, GFJ
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
干预措施: Fexofenadine (Drug)
结局指标
主要结局
Primary Pharmacokinetic Measure: Area Under the Curve (AUC)
时间窗: 0-72 hours
次要结局
未报告次要终点