Phase 1
N=24
Drug - Drug Interaction Study Between Quinine Sulfate and Theophylline
Pharmacokinetics
Bottom Line
View on ClinicalTrials.gov: NCT00779259 ↗Enrolled (actual)
24
Serious AEs
—
Results posted
Jul 2009
Primary outcome: Primary: Maximum Plasma Concentration(Cmax) — 9.58; 6.63; 9.81; 7.47 ug/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Theophylline 300mg (Drug); Quinine 648 mg (Drug); Theophylline 300 mg (Drug)
- Age
- Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Mutual Pharmaceutical Company, Inc.
- Primary completion
- Sep 2007
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Plasma Concentration(Cmax) |
9.58; 6.63; 9.81; 7.47 | — |
| PRIMARY Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] |
103.47; 45.17; 92.72; 51.68 | — |
| PRIMARY Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]. |
108.21; 96.88 | — |
| SECONDARY Electrocardiogram (ECG) Evaluation of the Maximum QT Interval Corrected for Heartrate (QTc), Quinine Study Day 11. |
453.33; 451.33 | — |
| SECONDARY Electrocardiogram (ECG) Evaluation of the Maximum QT Interval Corrected for Heartrate (QTc), Theophylline Co-administered With Quinine, Study Day 12. |
452; 455.33 | — |
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.
Data sourced from ClinicalTrials.gov (NCT00779259). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.