Pharmacokinetics of lomefloxacin in renally compromised patients

Abstract

The single-dose pharmacokinetics of orally administered lomefloxacin (400 mg) were studied in normal subjects and in patients with various degrees of renal function. The subjects were classified by creatinine clearance (CLCR) normalized for body surface area: group 1, CLCR of greater than 80 ml/min/1.73 m2; group 2, CLCR of 80 to greater than 40 ml/min/1.73 m2; group 3, CLCR of 40 to greater than 10 ml/min/1.73 m2; and group 4, CLCR of less than or equal to 10 ml/min/1.73 m2. Each group consisted of eight subjects. The pharmacokinetics of lomefloxacin were significantly influenced by renal function. There were significant differences in the elimination rate constant, half-life, area under the concentration-time curve from 0 h to infinity, apparent total drug clearance, renal clearance, and apparent nonrenal drug clearance between the four renal function groups. Mean half-lives for groups 1, 2, 3, and 4 were 8.09, 9.11, 20.90, and 44.25 h, respectively. There were no significant differences between the renal groups for maximum concentration of the drug in serum and apparent volume of distribution. Age had no apparent effect on lomefloxacin disposition. There was a significant relationship between CLCR and lomefloxacin total body clearance (r = 0.92, P = 0.001) and renal clearance (r = 0.94, P = 0.001). Despite a predominate renal route of elimination, nonrenal lomefloxacin clearance significantly decreased with decreasing renal function (r = 0.72, P = 0.001). Mean lomefloxacin excretion rates over 48 h were 60.7, 56.0, 29.1, and 1.0% of the administered dose for groups 1, 2, 3, and 4, respectively. Mean glucuronide excretion rates over 48 h were 7.8, 6.3, 10.0, and 0.6% of the administered dose for groups 1, 2, 3, and 4, respectively. Hemodialysis had no effect on lomefloxacin concentrations in plasma. In patients with normal to moderate renal function, 400 mg of lomefloxacin per day should provide therapeutic concentrations in blood. The lomefloxacin dose should be reduced to 200 mg/day as the CL(CR) falls below 30 ml/min/1.73 m2. No additional dosage adjustments appear to be necessary for hemodialysis patients.