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1 Enoxacin decreases the metabolic clearance of the bronchodilator theophylline not only in severely ill patients, but also in patients with stable chronic obstructive airways disease.2 In this comparative study, significantly increased plasma theophylline concentrations were measured during co-administration of enoxacin (110.9%) and, to a lesser degree, also during co-administration of pefloxacin (19.6%) and ciprofloxacin (22.8%). 3 Total body clearance of theophylline was significantly decreased by enoxacin (63.6%), ciprofloxacin (30.4%) and pefloxacin (29.4%). The pharmacokinetic parameters of theophylline did not change during co-administration of ofloxacin and nalidixic acid. 4 There is growing evidence that the observed interaction is caused not by the parent drugs, but by the 4-oxo metabolite of enoxacin, pefloxacin and ciprofloxacin.Keywords quinolone 4-oxo quinolone enoxacin pefloxacin ciprofloxacin ofloxacin nalidixic acid theophylline interaction lower respiratory tract infections

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In patients treated concurrently with theophylline and enoxacin, a new broad‐spectrum antibacterial agent of the quinolone class, unexpectedly high plasma theophylline concentrations were measured. In part I of this study, daily plasma theophylline concentrations were measured in 14 patients. The mean +/‐ s.d. theophylline concentrations increased from 8.5 +/‐ 2.8 micrograms ml‐1 prior to enoxacin to a maximum of 21.7 +/‐ 7.8 micrograms ml‐1 during coadministration. In part II, six of these patients received aminophylline intravenously at a constant infusion rate and under controlled conditions. Plasma theophylline concentrations rose from 8.4 +/‐ 2.4 micrograms ml‐1 prior to enoxacin treatment to 15.0 +/‐ 5.1 micrograms ml‐1 at day 3 of coadministration (P less than 0.005). Plasma protein‐binding and renal clearance of theophylline remained unchanged, whereas total body clearance of theophylline significantly decreased (P less than 0.005). From these observations it is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline. If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended.

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