Pharmacokinetics of levofloxacin during continuous veno-venous hemofiltration

Objective: To study the effect of continuous veno-venous hemofiltration (CVVHF) on the pharmacokinetics of levofloxacin in critically ill patients with 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 renal 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, filtrate substitution in post-dilution mode. Measurements and results: The plasma pharmacokinetics and clearance of levofloxacin by hemofiltration were established on day 1 and day 4-6 of treatment. Levofloxacin was determined by high-performance liquid chromatography (HPLC). Mean (range) peak plasma concentrations after levofloxacin 500 mg single 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/kg 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 clearance by hemofiltration 21 (13-27) ml/min, respectively. Conclusion: A dosage schedule of levofloxacin 250 mg qd with a 500 mg loading dose seems appropriate for anuric patients during CVVHF. Sufficiently high steadystate concentrations of levofloxacin were achieved after the first dose. Undesired accumulation of levofloxacin was not observed.