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Theophylline dosage adjustment during enoxacin coadministration
J R Koup1, R D Toothaker, E Posvar
1Department of Pharmacokinetics/Drug Metabolism, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Antimicrobial Agents and Chemotherapy
|May 1, 1990
Summary
Enoxacin significantly reduces theophylline clearance by about 50%. Reducing theophylline dosage by 50% during enoxacin use maintains stable plasma levels, but monitoring is advised.
Area of Science:
- Pharmacokinetics
- Drug Interactions
- Clinical Pharmacology
Background:
- Theophylline is a widely used bronchodilator with a narrow therapeutic index.
- Enoxacin, a fluoroquinolone antibiotic, is known to interact with theophylline metabolism.
- Previous studies indicated a significant reduction in theophylline clearance with enoxacin coadministration.
Purpose of the Study:
- To investigate the pharmacokinetic interaction between enoxacin and theophylline.
- To determine the appropriate theophylline dosage adjustment during enoxacin coadministration.
- To assess the impact of enoxacin withdrawal on theophylline plasma concentrations.
Main Methods:
- A sequential-design study involving seven healthy female volunteers.
- Administration of theophylline (200 mg b.i.d.) followed by coadministration with enoxacin (400 mg b.i.d.) with a reduced theophylline dose (100 mg b.i.d.).
- Theophylline dosage was adjusted after enoxacin discontinuation to observe rebound effects.
Main Results:
- Mean apparent theophylline clearance decreased by approximately 50% during enoxacin coadministration.
- A 50% reduction in theophylline dose maintained stable plasma concentrations during concurrent enoxacin therapy.
- Discontinuation of enoxacin led to a transient 35% increase in theophylline plasma levels within 24-48 hours.
Conclusions:
- A 50% theophylline dose reduction effectively manages plasma concentrations during enoxacin coadministration.
- Higher dose reductions (up to 75%) may be necessary for patients with high baseline theophylline clearance.
- Plasma theophylline monitoring is recommended when enoxacin therapy is required concurrently or upon its cessation.