Safety of fleroxacin coadministered with theophylline to young and elderly volunteers.

The influence of multiple doses of fleroxacin on the plasma clearance and the urinary excretion of theophylline was studied in 19 young and 18 elderly male volunteers. A theophylline dosage individualized to obtain a mean theophylline concentration in plasma of 10 +/- 3 micrograms/ml was administered for 1 week to each subject. At week 2, oral fleroxacin (400 mg once daily) was added. Theophylline concentrations in plasma were measured with TDx (Abbott Diagnostics, Mississauga, Ontario, Canada), and urinary excretion of theophylline and its three major metabolites was measured by high-performance liquid chromatography. Total theophylline clearance remained essentially unchanged throughout the study period (3.5 and 2.9 liters/h in the young and the elderly, respectively) both after a single fleroxacin dose and after multiple doses. Although significant changes occurred in the urinary excretion of unchanged theophylline and its metabolites after a single fleroxacin dose, no changes were observed after multiple doses. Side effects consisted mainly of gastrointestinal and sleep disturbances, more related to theophylline; photosensitivity was observed in six subjects and was attributed to fleroxacin. We conclude that fleroxacin may be administered concomitantly with theophylline in either young or elderly patients. Close monitoring of theophylline concentrations in serum should be performed, particularly in patients with chronic obstructive pulmonary disease, for whom data are currently lacking.