The Effect of Low Furanocoumarin Grapefruit Hybrid Juice Consumption on Midazolam Pharmacokinetics

Pharmacokinetics Clinical Trial

Official title:

The Effect of Low Furanocoumarin Grapefruit Hybrid Juice Consumption on Midazolam Pharmacokinetics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02117869
• Other study ID #: IRB201300728
• Status: Completed
• Phase: Phase 4
• First received: April 16, 2014
• Last updated: June 8, 2015
• Start date: May 2014
• Est. completion date: May 2015

Study information

• Verified date: June 2015
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Grapefruit (GF) contains furanocoumarin (FC) which is known to irreversibly inhibit the activity of cytochrome P450-3A (CYP3A) enzymes in the human gastrointestinal tract (PAINE 2005). Because CYP3A enzymes are integral in the metabolism of some drugs, co-ingesting GF or GF Juice (GFJ), which inhibits CYP3A, along with drugs reliant on CYP3A for metabolism can significantly alter the drugs kinetic properties and result in elevated plasma drug concentrations which may be toxic. The Citrus Research and Education Center at the University of Florida has developed a new GF hybrid (GFH) which contains low FC content and which may not inhibit CYP3A enzyme activity, and therefore may be safe to co-ingest with drugs that require CYP3A activity for metabolism. The investigators hypothesize that low FC GFHJ will not inhibit CYP3A to the degree that regular GFJ does, and will not significantly affect midazolam kinetics compared with regular GFJ. Midazolam is an FDA approved probe drug for CYP3A activity and has been used previously to establish an interaction between GFJ and midazolam. This study will evaluate the concomitant administration of midazolam and low FC GFHJ, regular GFJ, or water to evaluate the significance of this interaction.

Description:

As a participant in this study the following will take place: A pre-study visit will be done which will include a physical exam, pregnancy test if applicable, and a review of your medical history. If you qualify you will then undergo three separate study visits as described below.

While participating in this study, participants will not eat grapefruit or other citrus fruits (oranges, lemons, for example) or drink non-study specific grapefruit juice or other citrus fruit juices, or citrus containing foods (orange marmalade, for example) for 1 week prior to each study visit. In addition, no herbal or other dietary supplements or over the counter medications should be taken for 48 hours before and during the study visits.

During each of the three study visits, separated by at least 2 weeks, one of two different grapefruit juice products (either the low furanocoumarin grapefruit hybrid or regular grapefruit) or water will be provided. The order in which these three drinks will be received will be random, like the toss of a coin. Also, 1 dose of midazolam (a drug normally used to make someone sleepy or relaxed before a medical test) will be given during each visit.

Each study visit will consist of three days, on Days 1 and 2 a drink of 200ml (about 7 ounces) of the assigned grapefruit juice or water will be given.

On Day 3 of each study visit, you will fast (abstain from having anything to eat or drink except water) from 12 a.m. the night before, and report to the clinic for the study day at 8am.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 18-65 years of age

• non-smokers

Exclusion Criteria:

• Inability to abstain from alcoholic beverages (24 hours),

• Inability to abstain herbal containing supplements/teas/beverages, and

• Inability to abstain from over-the-counter medications (48 hours) prior to the study visits

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Other:
• Low furanocoumarin hybrid grapefruit juice
3 consecutive daily doses of 200ml low furanocoumarin grapefruit juice plus midazolam 5mg orally on the third day.
• Regular grapefruit juice
3 consecutive daily doses of 200ml regular grapefruit juice plus midazolam 5mg orally on the third day.
• Water (control)
3 consecutive daily doses of 200ml water plus midazolam 5mg orally on the third day.

Locations

Country	Name	City	State
United States	Clinical Research Center	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curves	For pharmacokinetic analysis, venous blood samples from an intravenous catheter in the arm will be collected prior to (0 hr, predose), and at 0.5, 1, 2, 3, 4, 6, and 9 hours after midazolam administration.	Approximately 9 hours	No
Secondary	Time to peak concentration	For pharmacokinetic analysis, venous blood samples from an intravenous catheter in the arm will be collected prior to (0 hr, predose), and at 0.5, 1, 2, 3, 4, 6, and 9 hours after midazolam administration.	Approximately 9 hours	No
Secondary	Peak concentration	For pharmacokinetic analysis, venous blood samples from an intravenous catheter in the arm will be collected prior to (0 hr, predose), and at 0.5, 1, 2, 3, 4, 6, and 9 hours after midazolam administration.	Approximately 9 hours	No