Elimination of levofloxacin in critically ill patients with renal failure: influence of continuous veno-venous hemofiltration.

Abstract

Pharmacokinetic data on levofloxacin in critically ill patients are sparse and conflicting. Aim of the study was to assess the clearance of levofloxacin in critically ill patients treated with continuous veno-venous hemofiltration (CVVH). Pharmacokinetics of levofloxacin were studied in 11 critically ill patients. Four patients were treated with CVVH because of renal failure, 4 patients had moderately impaired renal function but were not on hemofiltration, and 3 patients had approximately normal renal function. Patients received 0.5 g levofloxacin infused over 0.5 hours. Plasma levels of levofloxacin were determined by HPLC and pharmacokinetic parameters were calculated using a non-compartmental model. Levofloxacin clearance in critically ill patients with approximately normal renal function was similar to that in healthy subjects. In critically ill patients with impaired renal function not on CVVH, mean half-life was prolonged by a factor of about 3 (20-25 hours). The mean residence time and the volume of distribution were also increased. In renal failure treated with CVVH, a wide variability in pharmacokinetics was seen. The half-life was about 30 hours and the mean levofloxacin clearance was raised by a factor of 2. The area under the concentration-time curve was reduced by hemofiltration, while the volume of distribution was increased. There was a positive correlation between blood flow through the hemofilter and levofloxacin clearance. Variable amounts of the drug were recovered from the hemofilter. Most plasma levels, however, were in the therapeutic range and drug accumulation to toxic plasma concentrations was not observed in renal failure patients undergoing CVVH and receiving single daily administration of 0.5 g of levofloxacin i.v. During CVVH using polysulfone membrane hemofilters, plasma concentrations of levofloxacin are not easily predictable. Levofloxacin clearance may be affected by binding to secondary membranes formed in hemofilters during CVVH and blood flow rates have a significant impact on the pharmacokinetics of levofloxacin.