The pharmacokinetics of fleroxacin and its metabolites following a single oral dose of fleroxacin 400mg were examined in 6 healthy subjects and 24 patients with various degrees of renal insufficiency. Plasma and urine samples, collected at various times after administration, were assayed by high performance liquid chromatography (HPLC).In healthy subjects. Cmaxwas 6.8 ± 0.7 mg/L; tmax= about 1h, t½= 14 ± 2h, total clearance = 4.86 ± 0.72 L/h and the percentage of unchanged fleroxacin excreted in urine in 48 hours was 48 ± 4% (HPLC). Plasma concentrations of metabolites were very low and accounted for no more than 5% of the levels of unchanged fleroxacin.In uraemic patients Cmaxdid not change, whatever the degree of renal failure; tmaxwas increased in patients with a glomerular filtration rate below 0.6 L/h, and Vd/f was independent of the severity of renal failure. These data suggest that bioavailability of the drug is unchanged. In uraemic patients t½was prolonged and AUC multiplied by a factor of 2 to 3. A linear relationship was found between total and renal clearances of fleroxacin and creatinine clearance. Accumulation ofN-demethyl-fleroxacin andN-oxide-fleroxacin was very high in uraemic patients, due to slow formation of these metabolites and decreased urinary elimination.Dialysance of fleroxacin and of its metabolites was approximately 3.6 to 4.8 L/h. These findings suggest that fleroxacin dosage may need to be reduced in patients with severe renal disease; in haemodialysed patients, treated every 2 days, a single dose of fleroxacin 400mg is recommended at the end of each dialysis session.