PHARMACOKINETICS OF RUFLOXACIN IN PATIENTS WITH IMPAIRED RENAL-FUNCTION

The pharmacokinetics of rufloxacin were investigated in normal subjects and in patients with various degrees of renal failure after the administration of a single oral 400-mg dose. Twenty-four subjects were classified by glomerular filtration rate (GFR) normalized for body surface area. Group 1 subjects had GFRs of >80 ml/min, group 2 subjects had GFRs from 30 to 80 ml/min, group 3 subjects had GFRs from 8 to 29 ml/min, and group 4 subjects had GFRs of <8 ml/min. The patients in group 4 were on continuous peritoneal dialysis or underwent hemodialysis 48 h after dosing. Plasma and urinary rufloxacin concentrations were determined by high-performance liquid chromatography. A two-compartment model was used to calculate rufloxacin pharmacokinetic parameters. Apparent total body clearance of the drug was linearly related to GFR (r = 0.696; P < 0.01). The elimination half-life increased proportionally with the severity of renal impairment, with values of 30 +/- 3, 36 +/- 5, and 44 +/- 3 h in groups 1, 2, and 3, respectively. In patients undergoing dialysis (group 4), the elimination half-life (27 +/- 4 h) was not significantly different form that of controls, probably because of the clearance effect of dialysis. The renal clearances of rufloxacin decreased linearly with the decrease in GFR (r = 0.842; P < 0.01). The 0- to 96-h cumulative urinary recoveries of rufloxacin were 33 +/- 3, 27 +/- 3, 14 +/- 2, and 1 +/- 1% of the administered dose in groups 1, 2, 3, and 4, respectively. In patients with moderate renal failure, dosage adjustment of rufloxacin is not needed. The rufloxacin dose interval should be prolonged to 48 h as the GFR falls below 30 ml/min/1.73 m2.