A Drug-Food Interaction Study Between Colchicine and Grapefruit Juice
Condition: Pharmacokinetics
Study type: Interventional
Phase: Phase 1

Summary: 
      Grapefruit juice is an inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the
      enzyme systems responsible for the metabolism of colchicine. This study will evaluate the
      effect of multiple daily consumptions of grapefruit juice on the pharmacokinetic profile of a
      single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and
      tolerability of this regimen in healthy volunteers. All study subjects will be monitored for
      adverse events throughout the study period.
    

Detailed description: 
      Grapefruit juice is an inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the
      enzyme systems responsible for the metabolism of colchicine. This study will evaluate the
      effect of multiple daily consumptions of grapefruit juice on the pharmacokinetic profile of a
      single 0.6 mg dose of colchicine. On study Day 1, after a fast of at least 10 hours
      twenty-two healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of
      18 and 45 will be given one dose of colchicine (1 x 0.6 mg tablet). Fasting will continue for
      4 hours after the dose. Blood samples will be drawn from all participants before dosing and
      for 24 hours post-dose on a confined basis at times sufficient to adequately define the
      pharmacokinetics of colchicine. Blood sampling will continue on a non-confined basis on Days
      2-5. After a 14 day washout period, starting on the morning of Day 15 and continuing through
      Day 17, subjects will return to the clinic for consumption of an administered dose of
      grapefruit juice (1 x 240 ml) twice daily. On the morning of Day 18 after a fast of at least
      10 hours all subjects will receive a co-administered single oral dose of colchicine (1 x 0.6
      mg) and grapefruit juice (1 x 240 ml). Fasting will continue for 4 hours after the dose.
      Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on
      a confined basis at times sufficient to adequately define the pharmacokinetics of colchicine
      in the presence of grapefruit juice. Blood sampling will continue on a non-confined basis on
      Days 19-22. Subjects will consume the final administered dose of grapefruit juice (1 x 240
      ml) in the evening on Day 18. A further goal of this study is to evaluate the safety and
      tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout
      participation in the study for adverse reactions to the study drug and/or procedures. Seated
      blood pressure and pulse will be measured prior to dosing and at approximately 1, 2, and 3
      hours following drug administration on Days 1 and 18 to coincide with peak plasma
      concentrations of colchicine. All adverse events whether elicited by query, spontaneously
      reported, or observed by clinic staff will be evaluated by the Investigator and reported in
      the subject's case report form.
    

Intervention name(s): Colchicine; Grapefruit Juice; Colchicine
Intervention type(s): Drug; Other; Drug
Intervention description(s): A single dose of 0.6 mg colchicine administered alone at 7:15 a.m. on Day 1; 240 mL of grapefruit juice ingested twice daily at 7:15 a.m. and 7:15 p.m. on Days 15 to 18.; A single dose of 0.6 mg colchicine administered with grapefruit juice at 7:15 a.m. on Day 18 after an overnight fast of at least 10 hours.
Other intervention name(s): COLCRYS™
Intervention MeSH terms: Colchicine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: healthy; pharmacokinetics; grapefruit juice; furanocoumarins; cytochrome p450 3A4