Pharmacokinetics of levofloxacin during continuous venovenous hemodiafiltration and continuous venovenous hemofiltration in critically ill patients

Study Objective. To assess the pharmacokinetics of levofloxacin during continuous venovenous hemodiafiltration (CVVHDF) and continuous venovenous hemofiltration (CVVH). Design. Nonrandomized pharmacokinetic evaluation. Setting. University surgical intensive care unit. Patients. Six critically ill patients. Intervention. Five patients received levofloxacin 500 mg/day and one patient received levofloxacin 125 mg/day. All patients received continuous renal replacement therapy: CVVHDF on day 1 and CVVH on day 2, using an acrylonitrile hollow-fiber 0.9-m² filter, constant blood flow rate of 90 ml/minute, substitution flow rate of 1 L/hour predilution, and dialysate flow rate of 1 L/hour (CVVHDF). Measurements and Main Results. Serum, ultrafiltrate, and dialysate concentrations of levofloxacin were determined by high-performance liquid chromatography. Extracorporeal clearance was 26.05 ± 4.66 ml/hour during CVVHDF and 15.71 ± 2.73 ml/hour during CVVH (p<0.05). Elimination half-life was 28.08 ± 4.5 hours and 45.9 ± 17.7 hours, and distribution volume was 1.51 ± 0.52 L/kg and 1.42 ± 0.42 L/kg for CVVHDF and CVVH, respectively. Saturation was 0.76 ± 0.13 for CVVHDF versus a sieving coefficient of 0.77 ± 0.16 for CVVH. Conclusion. Marked extracorporeal elimination of levofloxacin occurs, requiring a dosage adjustment that can be calculated from the characteristics of CVVH and CVVHDF.