Drug-Food Interaction Study of Seville Orange Juice and Colchicine
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      Seville orange juice is an inhibitor of the intestinal cytochrome P450 (CYP) 3A4 enzyme, one
      of the enzymes responsible for the metabolism of colchicine. This study will evaluate the
      effect of multiple daily consumptions of Seville orange 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: 
      Seville orange juice is an inhibitor of the intestinal cytochrome P450 (CYP) 3A4 enzyme, one
      of the enzymes responsible for the metabolism of colchicine. This study will evaluate the
      effect of multiple daily consumptions of Seville orange juice on the pharmacokinetic profile
      of a single 0.6 mg dose of colchicine. Twenty-four 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) on Day 1, after an overnight fast. 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 to adequately define the baseline pharmacokinetics of colchicine. 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 240 ml dose of Seville
      orange juice in the morning and evening. At 8am on Day 18 after an overnight fast, all
      subjects will receive a co-administered single oral dose of colchicine (1 x 0.6 mg) and
      Seville orange 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 to
      adequately define the pharmacokinetics of colchicine in the presence of Seville orange juice.
      Subjects will consume the final administered 240 ml dose of Seville orange juice 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; Seville Orange Juice
Intervention type(s): Drug; Other
Intervention description(s): A single dose of 0.6 mg colchicine administered alone in the morning on Day 1 and a single dose of 0.6 mg colchicine administered with Seville orange juice in the morning on Day 18 after an overnight fast of at least 10 hours.; 240 mL of Seville orange juice administered in the morning and evening on Days 15 to 18.
Intervention MeSH terms: Colchicine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: blood levels over time; colchicine; seville orange juice; pharmacokinetics