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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02117869
Recruitment Status : Completed
First Posted : April 21, 2014
Last Update Posted : June 10, 2015
Sponsor:
Information provided by (Responsible Party):
University of Florida

Brief 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.

Condition or disease Intervention/treatment Phase
Pharmacokinetics Other: Low furanocoumarin hybrid grapefruit juice Other: Regular grapefruit juice Other: Water (control) Phase 4

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Official Title: The Effect of Low Furanocoumarin Grapefruit Hybrid Juice Consumption on Midazolam Pharmacokinetics
Study Start Date : May 2014
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Low furanocoumarin hybrid grapefruit juice
3 consecutive daily doses of 200ml low furanocoumarin hybrid grapefruit juice plus midazolam 5mg orally on the third day.
Other: Low furanocoumarin hybrid grapefruit juice
3 consecutive daily doses of 200ml low furanocoumarin grapefruit juice plus midazolam 5mg orally on the third day.

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




Primary Outcome Measures :
  1. Area under the plasma concentration-time curves [ Time Frame: Approximately 9 hours ]
    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.


Secondary Outcome Measures :
  1. Time to peak concentration [ Time Frame: Approximately 9 hours ]
    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.

  2. Peak concentration [ Time Frame: Approximately 9 hours ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02117869


Locations
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United States, Florida
Clinical Research Center
Gainesville, Florida, United States, 32611
Sponsors and Collaborators
University of Florida
Investigators
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Principal Investigator: Rhonda M Copper-DeHoff, PharmD, MS University of Florida

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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02117869    
Other Study ID Numbers: IRB201300728
First Posted: April 21, 2014    Key Record Dates
Last Update Posted: June 10, 2015
Last Verified: June 2015
Keywords provided by University of Florida:
Grapefruit juice
Additional relevant MeSH terms:
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Midazolam
Furocoumarins
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Photosensitizing Agents