A 60-year-old man on maintenance theophylline for COPD is started on ciprofloxacin for infective exacerbation. Three days later he develops coarse tremors, tachycardia, and a generalised seizure. His theophylline level is 34 micrograms/mL. What is the mechanism of this presentation?

• A Additive neuromuscular blockade by the fluoroquinolone
• B Inhibition of CYP1A2 mediated theophylline metabolism ✓
• C Displacement of theophylline from albumin binding sites
• D Reduced renal clearance of the unchanged drug

Explanation

Theophylline is inactivated mainly by hepatic cytochrome P450, particularly CYP1A2, with less than 15 percent excreted unchanged in urine. Fluoroquinolones such as ciprofloxacin and macrolides such as erythromycin inhibit this metabolism, raising levels into the toxic range where seizures and cardiac arrhythmias occur. Protein-bound displacement contributes little because theophylline is only moderately bound, and renal clearance of parent drug is minor.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.

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