Drug-Drug Interaction Study of Qualaquin and Midazolam
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This is an open label non-randomized single sequence, single group two way drug interaction
      study in healthy adult volunteers to determine the extent to which quinine, an inducer of
      cytochrome p450 CYP 3A4, affects the pharmacokinetics of midazolam, an accepted probe drug
      for CYP 3A4. The study will also determine the extent to which midazolam affects the
      pharmacokinetics of quinine.
    

Detailed description: 
      This is an open label single sequence single group non-randomized two way drug interaction
      study in healthy adult volunteers to determine the extent to which quinine, an inducer of
      cytochrome p450 CYP 3A4, affects the pharmacokinetics of midazolam, an accepted probe drug
      for CYP 3A4. The study will also determine the extent to which midazolam affects the
      pharmacokinetics of quinine. This will compare the pharmacokinetics of midazolam and quinine
      at baseline to their kinetics when they are taken together in 24 normal healthy adult
      volunteers who will serve as their own controls. All patients will be confined to the study
      site throughout the entire 11 day study period. On day 1 after a fast of at least 10 hours,
      all study participants will receive a single oral dose of midazolam 2 mg. Blood will be drawn
      at times sufficient to adequately define the baseline concentration time curve for midazolam
      and its metabolite, 1-hydroxy-midazolam. On the morning of day 4, after a 3 day washout
      period and following a fast of at least 10 hours, all volunteers will begin a regimen of 324
      mg of quinine sulfate by mouth every 8 hours. All subjects will continue this regimen from
      day 4-10 (21 total doses). Blood will be drawn after the first daily dose of quinine on days
      4 and 9 at times sufficient to adequately define the baseline and steady state concentration
      time curves for quinine. Additional blood will be drawn prior to the first daily dose of
      quinine on days 7,8,9,and 10. On day 10 after a fast of at least a 10 hours, all participants
      will receive both midazolam 2 mg and quinine 324 mg together. Blood will be drawn a times
      sufficient to characterize the pharmacokinetics of midazolam, 1-hydroxy-midazolam and quinine
      under the stated conditions.
    

Intervention name(s): Midazolam Alone; Qualaquin (quinine) alone steady state; Midazolam and Qualaquin at steady state
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Midazolam 2 mg syrup was given orally after a fast of at least 10 hours.; Qualaquin (quinine) 324 mg capsules were given orally every 8 hours for 7 days ( 21 doses total). On day 9 after taking Qualaquin (quinine) for 5 days according to the stated regimen and fasting for at least 10 hours, all participants took their usual dose of Qualaquin (quinine). Blood was drawn at times sufficient to characterize the pharmacokinetics of quinine at steady state; On the morning of day 10 after taking Qualaquin (quinine) for 6 days according to the stated regimen (324 mg every 8 hours), all participants took their usual dose of Qualaquin (quinine) with an oral dose of midazolam 2 mg after a fast of at least 10 hours
Other intervention name(s): Midazolam; Qualaquin, Quinine Sulfate; midazolam, Qualaquin, quinine sulfate
Intervention MeSH terms: Quinine; Midazolam
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: midazolam; drug interactions; cytochrome p450