title: Metabolism of fleroxacin in man.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Essen, Federal Republic of Germany.
authors.forename: F
authors.initials: F
authors.lastname: Sörgel
authors.forename: R
authors.initials: R
authors.lastname: Seelmann
authors.forename: K
authors.initials: K
authors.lastname: Naber
authors.forename: R
authors.initials: R
authors.lastname: Metz
authors.forename: P
authors.initials: P
authors.lastname: Muth
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000378:metabolism*; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000378:metabolism; D016576:Fleroxacin; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male
chemical_list: D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D016576:Fleroxacin