Pharmacokinetics of linezolid in subjects with renal dysfunction

Abstract

Linezolid is a member of a new, unique class of synthetic antibacterial agents called oxazolidinones that are effective against gram-positive bacteria, including vancomycin-resistant organisms. We tested the hypothesis that the linezolid clearance would not be altered in subjects with renal dysfunction. Twenty-four subjects with renal function that ranged from normal to severe chronic impairment were enrolled, including patients with end-stage renal disease who were maintained on hemodialysis. Hemodialysis subjects were studied while they were both on and off dialysis. Linezolid was administered as a single oral 600-mg dose, and plasma and urine samples were assayed for linezolid and metabolites for 48 h for all subjects and for up to 96 h for those subjects with impaired renal function not on dialysis. The total apparent oral clearance of linezolid did not change with renal function and ranged from 92.5 to 109.6 ml/min for subjects not requiring dialysis. For subjects on dialysis, the total apparent oral clearance increased from 76.6 ml/min on their off-dialysis day to 130.0 ml/min on their on-dialysis day. Approximately one-third of the dose was removed by dialysis. However, those subjects with severe renal insufficiency (creatinine clearance, <40 ml/min) and those with end-stage renal disease maintained on hemodialysis had higher concentrations of both metabolites. We conclude that no adjustment of the linezolid dosage is needed in subjects with renal dysfunction or subjects on hemodialysis.

FIG. 1.

Plots of the mean serum linezolid concentration over time for the subjects, by group. Group 1, CL_CR, >80 ml/min; group 2, CL_CR, 40 to 80 ml/min; group 3, CL_CR, 10 to 39 ml/min; group 4, hemodialysis patients.

FIG. 2.

Plots of mean serum linezolid concentrations over time for hemodialysis subjects while off dialysis and on dialysis.

FIG. 3.

Regression plot of the oral linezolid clearance versus the measured CL_CR at the time of dosing for all subjects in the study. The line represents the regression line of those data.