Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction?

University of North Carolina (UNC)

Status: Completed

Conditions: Food-drug Interaction

Treatments: Drug: Fexofenadine

Study type: Interventional

Funder types: Other

Identifiers

NCT01526213

IRB 09-0788

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

18 participants in 6 patient groups

Sequence 1: Water, GFJ, FC-free GFJ

Other group

Description:

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.

Treatment:

Drug: Fexofenadine

Sequence 2: Water, FC-free GFJ, GFJ

Other group

Description:

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.

Treatment:

Drug: Fexofenadine

Sequence 3: GFJ, FC-free GFJ, Water

Other group

Description:

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.

Treatment:

Drug: Fexofenadine

Sequence 4: GFJ, Water, FC-free GFJ

Other group

Description:

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.

Treatment:

Drug: Fexofenadine

Sequence 5: FC-free GFJ, GFJ, Water

Other group

Description:

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.

Treatment:

Drug: Fexofenadine

Sequence 6: FC-free GFJ, Water, GFJ

Other group

Description:

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.

Treatment:

Drug: Fexofenadine