Pharmacokinetics of levofloxacin during continuous veno-venous hemofiltration

Objective: To study the effect of continuous veno-venous hemofiltration (CV VHF) on the pharmacokinetics of levofloxacin in critically ill patients wit h acute renal failure. Design: Open-label study. Setting: Anesthesiology ICU, University Hospital of Regensburg. Patients: Six critically ill patients treated with CVVHF because of acute r enal failure needing antimicrobial therapy. Interventions: Levofloxacin i. v. 250 mg qd with a starting dose of 500 mg. CVVHF with the following characteristics: hemofilter AN69 hollow fibers of 0.90 m(2) area, blood flow 150 ml/min, ultrafiltrate flow 1.3 l/h, filtrat e substitution in post-dilution mode. Measurements and results: The plasma pharmacokinetics and clearance of levo floxacin by hemofiltration were established on day 1 and day 4-6 of treatme nt. Levofloxacin was determined by high-performance liquid chromatography ( HPLC). Mean (range) peak plasma concentrations after levofloxacin 500 mg si ngle dose (s.d.) and 250 mg multiple dose (m.d.) were 6.4 (2.7-9.3) and 8.2 (4.7-10.3) mg/l, trough levels 2.7 (1.4-5.0) and 2.9 (1.7-3.9) mg/l, half- life 28 (19-38) and 22 (17-31) h, volume of distribution 1.2 (0.72-1.6) l/k g and 0.91 (0.52-2.0) l/kg, respectively. The mean sieving coefficient was 0.96 (0.79-1.09), mean total clearance 47 (20-89) ml/min, and mean clearanc e by hemofiltration 21 (13-27) ml/min, respectively. Conclusion: A dosage schedule of levofloxacin 250 mg qd with a 500 mg loadi ng dose seems appropriate for anuric patients during CVVHF. Sufficiently hi gh steadystate concentrations of levofloxacin were achieved after the first dose. Undesired accumulation of levofloxacin was not observed.