Drug-Drug Interaction Study Between Quinine Sulfate and Rosiglitazone
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      Rosiglitazone is predominantly metabolized by cytochrome P450 (CYP) 2C8. Quinine sulfate is
      an inhibitor of CYP 2C8. This study will evaluate the effect of multiple doses of quinine
      sulfate at steady-state on the pharmacokinetics of single-dose rosiglitazone in healthy adult
      subjects.
    

Detailed description: 
      Rosiglitazone is predominantly metabolized by cytochrome P450 (CYP) 2C8. Quinine sulfate is
      an inhibitor of CYP 2C8. This study will evaluate the effect of multiple doses of quinine
      sulfate at steady-state on the pharmacokinetics of single-dose rosiglitazone in healthy adult
      subjects.

      On study Day 1 after a fast of at least 10 hours, twenty four healthy, non-smoking,
      non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one oral
      dose of rosiglitazone (1 x 4 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 at
      times sufficient to adequately define the pharmacokinetics of rosiglitazone. A 2 day washout
      period will be completed after the first dose of rosiglitazone on Day 1. On Days 4-7 all
      subjects will receive a dose of quinine sulfate (2 x 324 mg capsules) every 8 hours starting
      with the 7:15 a.m. dose on Day 4 and continuing through the 11:15 p.m. dose on Day 7. Doses
      of quinine sulfate on Days 4-6 will be administered without regard to meals. On the morning
      of Day 7 after an overnight fast of at least 10 hours, all study participants will receive
      co-administered doses of rosiglitazone (1 x 4 mg tablet) and quinine sulfate (2 x 324 mg
      capsules). 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 at times sufficient to adequately
      determine the pharmacokinetics of rosiglitazone. 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. Blood pressure (sitting for at least 3 minutes) and pulse will be measured prior
      to dosing and at 1, 2 and 3 hours after the morning dose of rosiglitazone on Days 1 and 7.
      Electrocardiograms (EKG) will be recorded on Day 4 before dosing of quinine sulfate and at 1,
      2 and 4 hours post-dose and on Day 7 before the co-administered doses of rosiglitazone and
      quinine sulfate and at 1, 2 and 4 hours post-dose. 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): Rosiglitazone 4 mg Tablets; Rosiglitazone 4 mg Tablets; Quinine Sulfate 324 mg Capsules
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Rosiglitazone 4 mg tablet administered as a single oral dose on the morning of Day 1.; Co-administered single oral doses of rosiglitazone 4 mg (1 x 4 mg tablet) and quinine sulfate 648 mg (2 x 324 mg capsules) on the morning of Day 7.; Co-administered single oral doses of rosiglitazone 4 mg (1 x 4 mg tablet) and quinine sulfate 648 mg (2 x 324 mg capsules) on the morning of Day 7.
Other intervention name(s): Avandia®; Avandia®; Qualaquin®
Intervention MeSH terms: Rosiglitazone; Quinine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: rosiglitazone; quinine sulfate; drug interactions; cytochrome p450