The theophylline‐enoxacin interaction: II. Changes in the disposition of theophylline and its metabolites during intermittent administration of enoxacin

The pharmacokinetics of theophylline and its three major metabolites, 3-methylxanthine, 1-methylurate, and 1,3-dimethylurate, were studied during intermittent administration of enoxacin. The addition of enoxacin (400 mg, twice daily) to a theophylline dosing regimen (150 mg, twice daily) resulted in an immediate fall in plasma theophylline metabolite concentrations. Mean steady-state theophylline concentration in plasma during the dosing interval increased from 3.17 to 8.23 µg/ml. The mean 12-hour recovery of total theophylline metabolite decreased from 76.3 to 38.6 mg. After the discontinuation of enoxacin, but not theophylline, the plasma theophylline metabolite levels immediately increased to near or above the concentrations observed before enoxacin coadministration. Concurrently, theophylline concentrations decreased to levels equivalent to those observed before enoxacin coadministration. In general, the changes in plasma theophylline concentrations observed after the addition or discontinuation of enoxacin were complete within 3 days. Clinical Pharmacology and Therapeutics (1989) 46, 420–428; doi:10.1038/clpt.1989.160