Interaction between Methadone and Ciprofloxacin

The cytochrome P450 (CYP450) system comprises more than 40 individual enzymes that have been identified in humans. Six major CYP450 isoenzymes are responsible for more than 90% of oxidation of drugs in humans: 1A2, 3A4, 2C9, 2C19, 2D6, and 2E1. Methadone is metabolized by several CYP450 isoenzymes (1A2, 3A4, 2B6, 2C8, 2C9, 2C19, and 2D6) to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), an inactive metabolite. CYP3A4 is considered the primary isoenzyme responsible for metabolism, followed by CYP2D6. Various drugs may inhibit the CYP450 system. Among the quinolone antibiotics, ciprofloxacin has been demonstrated in vitro to be one of the more potent of these inhibitors, affecting in particular CYP1A2 and CYP3A4. However, the clinical response is sometimes difficult to predict, and the significance of the interaction differs among patients. This report describes a patient who was receiving a stable dose of methadone for treatment of heroin addiction and in whom severe respiratory depression developed after initiation of ciprofloxacin for aspiration pneumonia.