The Effect of Low Furanocoumarin Grapefruit Hybrid Juice Consumption on Midazolam Pharmacokinetics
Condition: Pharmacokinetics
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Low furanocoumarin hybrid grapefruit juice; Regular grapefruit juice; Water (control)
Intervention type(s): Other; Other; Other
Intervention description(s): 3 consecutive daily doses of 200ml low furanocoumarin grapefruit juice plus midazolam 5mg orally on the third day.; 3 consecutive daily doses of 200ml regular grapefruit juice plus midazolam 5mg orally on the third day.; 3 consecutive daily doses of 200ml water plus midazolam 5mg orally on the third day.
Intervention MeSH terms: Furocoumarins
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Keywords: Grapefruit juice