Interaction between the fluoroquinolones and the bronchodilator theophylline

Area of Science:

• Pharmacology
• Drug Interactions
• Respiratory Medicine

Background:

• Fluoroquinolone antibiotics like ofloxacin are used for respiratory tract infections.
• Other fluoroquinolones (enoxacin, ciprofloxacin, pefloxacin) significantly reduce theophylline clearance.
• Theophylline toxicity has been reported with concomitant use of these agents.

Purpose of the Study:

• To review available data on the interaction between ofloxacin and theophylline metabolism.
• To compare the metabolic effects of ofloxacin with other fluoroquinolones on theophylline.

Main Methods:

• Review of existing clinical data and pharmacokinetic studies.
• In vitro studies investigating the mechanism of interaction with cytochrome P450 enzymes.
• Animal studies (rats) with high concentrations of ofloxacin.

Main Results:

• Unlike other fluoroquinolones, ofloxacin did not lead to increased theophylline plasma concentrations or toxicity signs in humans.
• Enoxacin, ciprofloxacin, and pefloxacin caused significant (60% and 30%) reductions in theophylline clearance.
• Quinolones interact with cytochrome P450 enzymes, inhibiting theophylline demethylation.
• Ofloxacin showed minimal effect on these enzymes in rats at high doses and no significant effect in humans at therapeutic doses (up to 800 mg/day).

Conclusions:

• Ofloxacin does not pose a significant risk of theophylline toxicity due to drug interactions.
• Clinicians can safely co-administer ofloxacin and theophylline.
• Further research confirmed the lack of clinically relevant metabolic interaction between ofloxacin and theophylline.