Single and multiple dose pharmacokinetics of fleroxacin

Pharmacokinetics of fleroxacin following single and multiple dosing were studied in healthy male volunteers. The characteristics of this new trifluorinated quinolone are the long elimination half-life of approximately 10 h and the high plasma concentrations, which exceed 2 mg/l after an oral dose of 200 mg. These two parameters are a prerequisite for a once daily dosage regimen. A good linear relationship (r = 0.998) was found between administered doses (100-2500 mg) and resulting AUC values. The volume of distribution (Vss) exceeded 1 l/kg and reflects the good tissue penetration. Renal clearance of unbound drug was 104 ml/min and within three days 56% of the dose could be recovered from urine as unchanged drug. Multiple dosing of 800 or 1200 mg fleroxacin once daily over ten days resulted in an accumulation of the drug in the plasma by a factor of 1.4. This value is in agreement with the theoretically predicted accumulation and thus non-linear, time-dependent pharmacokinetics can be excluded. The administered tablets were completely bioavailable (F = 1.0) and a significant first pass metabolism can therefore be excluded.