Metabolism of fleroxacin in man.

The metabolism of fleroxacin was studied in 12 healthy volunteers by use of a newly developed high pressure liquid chromatographic assay. Desmethylfleroxacin and fleroxacin N-oxide were identified as the major metabolites of fleroxacin in plasma and urine. The maximum concentrations of fleroxacin, desmethylfleroxacin and fleroxacin N-oxide in plasma were 5.2 +/- 1.1, 0.0683 +/- 0.0151 and 0.0634 +/- 0.0090 mg/l reached at 1.2 +/- 0.7 h, 2.2 +/- 0.8 h and 6.2 +/- 2.4 h respectively (one subject excluded from analysis). The plasma AUC was between 1.0 and 2.6 mg.h/l for either metabolite and between 47.9 and 75.1 mg.h/l for the parent compound. The terminal half-life of desmethylfleroxacin was higher than that of unchanged fleroxacin and similar to the half-life of fleroxacin N-oxide. In urine unchanged fleroxacin, desmethylfleroxacin and fleroxacin N-oxide accounted for 59.9%, 6.8% and 6.3% of the dose of fleroxacin. The renal clearance of fleroxacin, desmethylfleroxacin and fleroxacin N-oxide were 67.6, 300.9 and 324.8 ml/min respectively. We conclude that demethylation and N-oxidation of fleroxacin affects the distribution and elimination characteristics significantly. Renal clearance increased, and it is suggested that the volume of distribution may increase also.