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Drug-drug interactions affecting fluoroquinolones
G J Wijnands1, T B Vree, T J Janssen
1Department of Pulmonary Diseases, Foundation of Deventer Hospitals, The Netherlands.
The American Journal of Medicine
|December 29, 1989
Summary
Enoxacin significantly slows theophylline metabolism by inhibiting N-demethylation, increasing its half-life. Ofloxacin had no significant effect on theophylline metabolism or excretion in healthy volunteers.
Area of Science:
- Pharmacology
- Drug Metabolism
Background:
- Theophylline is a bronchodilator with known metabolic pathways.
- Quinolone antibiotics can interact with drug-metabolizing enzymes.
Purpose of the Study:
- To investigate the impact of ofloxacin and enoxacin on theophylline metabolism in healthy volunteers.
Main Methods:
- A three-week study involving two healthy volunteers receiving intravenous aminophylline.
- Theophylline was administered alone (control), with ofloxacin, and with enoxacin.
- Metabolite analysis focused on C-8 oxidation and N-demethylation products.
Main Results:
- Enoxacin significantly increased theophylline's elimination half-life and decreased its total body clearance.
- Enoxacin reduced the formation of N-demethylation metabolites (1-methyluric acid, 3-methylxanthine) but less affected C-8 oxidation metabolites.
- Ofloxacin did not alter theophylline's plasma parameters or renal excretion.
Conclusions:
- Enoxacin inhibits theophylline's microsomal N-demethylation pathway, leading to reduced metabolic clearance.
- Ofloxacin does not significantly interfere with theophylline disposition.