Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction?

Food-drug Interaction Clinical Trial

Official title:

Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01526213
• Other study ID #: IRB 09-0788
• Status: Completed
• Phase: N/A
• First received: January 31, 2012
• Last updated: December 29, 2012
• Start date: September 2009
• Est. completion date: April 2011

Study information

• Verified date: December 2012
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: April 2011
• Est. primary completion date: April 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Food-drug Interaction

Intervention

Drug:
• Fexofenadine
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, or furanocoumarin-free grapefruit juice.

Locations

Country	Name	City	State
United States	North Carolina Clinical and Translational Research Center	Chapel Hill	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Pharmacokinetic Measure: Area Under the Curve (AUC)		0-72 hours	No