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Pharmacokinetics of Moxifloxacin and Levofloxacin in Intensive Care Unit Patients Who Have Acute Renal Failure and Undergo Extended Daily Dialysis

David Czock^*, Cordula Hüsig-Linde, Anita Langhoff, Timo Schöpke, 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

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{at}yahoo.com

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.

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