Drug-Drug Interaction Study of Qualaquin and Midazolam
Condition: Healthy
Intervention: Midazolam Alone; Qualaquin (quinine) alone steady state; Midazolam and Qualaquin at steady state
Intervention description: 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
Intervention MeSH terms: Quinine; Midazolam
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: midazolam; drug interactions; cytochrome p450

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Medically healthy non-smoking, non-obese (≥ 60 kg males, ≥52 kg females within 15% of
             IBW) adult volunteers 18-45 years of age

        Exclusion Criteria:

          -  Subjects with history or presence of significant cardiovascular disease (including
             hypotension, hypertension, bradycardia or EKG abnormalities), pulmonary, hepatic,
             gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine,
             immunologic, dermatologic, neurologic, psychiatric disease or an active sexually
             transmitted disease.

          -  Subjects with significant blood loss in the prior 56 days, plasma donation within 7
             days , hemoglobin < 12.0 g/dl or who have participated in another clinical trial
             within the prior 30 days.

          -  Subjects with recent (2-year) history or evidence of alcoholism or drug abuse.

          -  Subjects who have used any drugs or substances known to inhibit or induce cytochrome
             P450 (CYP) enzymes 10 days or 28 days respectively prior to the first dose and
             throughout the study.

          -  Subjects who have received monoamine oxidase inhibitors or been on a special diet
             within 28 days of starting the study.

          -  Subjects who test positive at screening for human immunodeficiency virus (HIV),
             hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV).

        Subjects who are pregnant or lactating, taking hormone replacement therapy or have known
        allergies to quinine sulfate, mefloquine, quinidine or midazolam and other benzodiazepines.