A 58-year-old asthmatic on maintenance oral theophylline is started on ciprofloxacin for acute bacterial prostatitis. Four days later he develops nausea, tremor, and a wide-complex tachyarrhythmia. The most likely mechanism of this interaction is:

• A Inhibition of CYP1A2, reducing hepatic clearance of theophylline ✓
• B Inhibition of intestinal P-glycoprotein increasing theophylline absorption
• C Additive QT prolongation by the two drugs
• D Competition for renal tubular secretion raising theophylline levels

Explanation

Ciprofloxacin and enoxacin are potent inhibitors of CYP1B2, the principal enzyme metabolizing theophylline. Reduced hepatic clearance raises serum theophylline concentrations, producing nausea, CNS excitation, seizures, and arrhythmias. Theophylline is not a P-glycoprotein substrate handled this way, ciprofloxacin causes little QT prolongation compared with moxifloxacin or sparfloxacin, and theophylline is not primarily cleared by tubular secretion.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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