Pharmacokinetics of Moxifloxacin and Levofloxacin in Intensive Care Unit Patients Who Have Acute Renal Failure and Undergo Extended Daily Dialysis David Czock,* Cordula Hu ¨ sig-Linde, † Anita Langhoff, † Timo Scho ¨ pke, † Carsten Hafer, † Kirsten de Groot, † Stefanie Swoboda, ‡ Ernst Kuse, § Hermann Haller, † Danilo Fliser, † Frieder Keller,* and Jan T. Kielstein † *Division of Nephrology, University Hospital Ulm, Ulm, † Division of Nephrology and § Department of Abdominal and Transplant Surgery, Hannover Medical School, Hannover, and ‡ Pharmacy Department, University of Heidelberg, Heidelberg, Germany Extended daily dialysis (EDD) is increasingly popular in the treatment of acute renal failure (ARF). EDD could remove drugs to a much different degree compared with intermittent standard hemodialysis or continuous renal replacement therapies; however, there are only scarce data on how EDD influences the pharmacokinetics of frequently used drugs. The aim of this study was to determine the pharmacokinetics of two quinolone antibiotics in patients who had anuric ARF and were being treated with EDD. Adult patients who were in the intensive care unit at a tertiary care university hospital and receiving moxifloxacin (n  10) or levofloxacin (n  5) therapy were included. The antibiotics were administered intravenously 8 h (400 mg of moxifloxacin) or 12 h (500 mg of levofloxacin) before EDD to study pharmacokinetics off and on EDD. Treatment lasted 8 h; blood and dialysate flow rates were 160 ml/min. In addition to standard pharmacokinetic parameters, the total dialysate concentration of both drugs was measured using a technically simple single-pass batch dialysis system for EDD. Moxifloxacin pharmacokinetics in critically ill patients who had ARF and were undergoing EDD were similar to those in healthy subjects without renal impairment. Levofloxacin, although removed by EDD, had a lower total clearance compared with healthy subjects. According to these findings, anuric critically ill patients who are undergoing EDD should be treated with the standard dosage of moxifloxacin (400 mg/d intravenously). The levofloxacin dosage, however, should be reduced according to the intensity of renal replacement therapy. Clin J Am Soc Nephrol 1: 1263–1268, 2006. doi: 10.2215/CJN.01840506 F luoroquinolones have enjoyed enormous clinical suc- cess in the past 20 yr. The most widely used group II fluoroquinolones (ciprofloxacin and ofloxacin) exhibit activity mainly against Gram-negative bacteria. Recently, group III (levofloxacin) and group IV (moxifloxacin) fluoro- quinolones, which possess an improved activity against Gram- positive pathogens while maintaining similar activity against many Gram-negative bacteria, increasingly have been used (1). In intensive care unit (ICU) patients who have sepsis and multiple organ failure, extended daily dialysis (EDD) repre- sents an important extracorporeal renal replacement therapy that is increasingly used in ICU throughout Europe, the United States, and Brazil (2– 8). EDD could remove drugs to a much different degree compared with standard intermittent hemodi- alysis (IHD) three times a week or continuous renal replace- ment therapy (CRRT) (9). Nevertheless, only scarce data are available on the effect of this highly efficient renal replacement therapy on the elimination of frequently used drugs in critically ill patients with renal failure (10 –13). The aim of our study was to investigate the pharmacokinetics of moxifloxacin and levo- floxacin in anuric critically ill patients who were undergoing EDD. Because there is no reliable standard approach, we ap- plied various methods to estimate extracorporeal drug re- moval. Materials and Methods Patients and Study Protocol Adult ICU patients who had anuric acute renal failure (ARF) and were being treated with EDD and receiving either moxifloxacin (n = 10) or levofloxacin (n = 5) were enrolled. The choice of the antibiotic for each patient was made on clinical grounds. Patients were included into the study after informed consent had been obtained from the patient or the patient’s legal representative. Moxifloxacin (400 mg) was infused intravenously in 10 patients during a period of 60 min, 8 h before EDD was started. Because the plasma half-life of levofloxacin in renal failure is known to be substantially increased, levofloxacin (250 or 500 mg) was infused during a period of 60 min even 12 h before EDD was started. This approach was chosen to study the pharmacokinetics of the two drugs off and on dialysis in the same patient while avoiding interday variability. The study protocol was approved by the Hannover Medical Received May 27, 2006. Accepted August 21, 2006. Published online ahead of print. Publication date available at www.cjasn.org. D.C. and C.H.-L contributed equally to this work. Address correspondence to: Dr. Jan T. Kielstein, Department of Nephrology, Medical School Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Phone: +49-511-532-6319; Fax: +49-511-532-4005; E-mail: kielstein@yahoo.com Copyright © 2006 by the American Society of Nephrology ISSN: 1555-9041/106-1263