Drug - Drug Interaction Study Between Quinine Sulfate and Theophylline
Condition: Pharmacokinetics
Intervention: Theophylline 300mg; Quinine 648 mg; Theophylline 300 mg; Quinine 648 mg
Intervention description: Single doses of theophylline 300 mg as an immediate-release oral solution 80mg/15ml concentration administered alone at 7 am on Day 1 after an overnight fast of at least 10 hours and along with quinine sulfate (2 x 324 mg capsules) at 7am on Day 12 after an overnight fast of at least 10 hours.; 648 mg quinine sulfate(2 x 324 mg capsules) initiated at 3pm on Day 5 and taken every 8 hours through Day 11 and co-administered with theophylline 300 mg as an immediate-release oral solution 80 mg/15 ml concentration at 7am on Day 12.; Single doses of theophylline 300 mg as an immediate-release oral solution 80mg/15ml concentration administered alone at 7 am on Day 1 after an overnight fast of at least 10 hours and along with quinine sulfate (2 x 324 mg capsules) at 7am on Day 12 after an overnight fast of at least 10 hours.; 648 mg quinine sulfate(2 x 324 mg capsules) initiated at 3pm on Day 5 and taken every 8 hours through Day 11 and co-administered with theophylline 300 mg as an immediate-release oral solution 80 mg/15 ml concentration at 7am on Day 12.
Intervention MeSH terms: Quinine; Theophylline
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: Male
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: quinine sulfate; theophylline; drug interactions; cytochrome p450; humans; male; adult

Summary:

      In a prior in vitro study using human hepatocytes quinine was shown to induce the activity of
      Cytochrome p450 CYP 1A2. The present study will evaluate the extent to which quinine
      sulfate-related induction of this enzyme effects the pharmacokinetics of theophylline, a
      sensitive probe drug for the activity of CYP 1A2. It will also evaluate the effect of
      single-dose theophylline on the pharmacokinetics of steady-state quinine sulfate.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Medically healthy non-smoking, non-obese (≥ 55kg and within 15% of ideal body weight)
             adult male volunteers 18-45 years of age

        Exclusion Criteria:

          -  Subjects with history or presence of glucose 6 phosphate dehydrogenase deficiency,
             myasthenia gravis, optic neuritis, glaucoma or significant cardiovascular disease
             (including hypotension, 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 and/or P-glycoprotein within 30 days prior to the first dose and
             throughout 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 or have hypersensitivity to quinine sulfate,
             mefloquine, quinidine or hypersensitivity to theophylline or aminophylline.