Pharmacokinetics of fleroxacin in renal impairment.
Fleroxacin is excreted primarily via the kidneys in its unchanged form, and therefore renal impairment has a major influence on the pharmacokinetics of this drug. This study examined the pharmacokinetics of oral and intravenous fleroxacin in patients with renal impairment. Patients with renal disease (mean glomerular filtration rate [GFR], 22 mL/min) and healthy subjects (mean GFR, 100 mL/min) received 400 mg of fleroxacin orally and 100 mg of fleroxacin intravenously in a crossover design. Serial blood samples and a complete urine collection were obtained for > or = 72 hours after dosing. Unchanged drug in plasma and urine was determined by reverse-phase high-performance liquid chromatography. Fleroxacin was well tolerated by all study participants. Renal impairment had no influence on the complete absorption of fleroxacin from the gastrointestinal tract, the maximal plasma concentration, and the steady-state volume of distribution (Vd-ss > 1 L/kg). However, systemic clearance in patients was significantly decreased (p < 0.05) to 44.4 mL/min compared with 87.1 mL/min in healthy subjects. This decrease could be ascribed to a reduction in renal clearance from 59.1 mL/min in healthy subjects to 8.8 mL/min in patients. Metabolic clearance was not reduced significantly. As a consequence of reduced clearance, the mean elimination half-life in patients increased from 13.6 hours to 21.4 hours and the area under the concentration-time curve from 87.0 mg.h/L to 170.5 mg.h/L. To avoid an unacceptable accumulation of fleroxacin in the body during multiple dosing, the following dose adjustment was recommended: patients with renal disease whose GFR is < 40 mL/min should receive the normal loading dose, i.e., 400 mg, but should receive maintenance doses that are reduced by 50%, i.e., to 200 mg.
Weidekamm
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Department of Clinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D005260:Female; D016576:Fleroxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000378:metabolism*
D016576:Fleroxacin