Pharmacokinetics of intravenous polymyxin B in critically ill patients

Abstract

Background. Although not much pharmacokinetic knowledge is available, polymyxin B is increasingly used for treatment of infections caused by gram-negative bacteria that are resistant to all other antibiotics. Methods. This study involved 8 patients who received intensive care after intravenous administration of a 60-min infusion of polymyxin B at currently recommended doses. Blood and urine samples were collected, and plasma protein binding of polymyxin B was determined. Concentrations of polymyxin B in plasma and urine samples were measured by a specific high-performance liquid chromatographic method. Results. Polymyxin B was well tolerated. The peak plasma concentrations at the end of the infusion varied from 2.38 to 13.9 mg/L. For 4 patients from whom it was possible to collect urine samples over a dosing interval, only 0.04%-0.86% of the dose was recovered in the urine in unchanged form. Plasma protein binding of polymyxin B was higher in samples from patients (range, 78.5%-92.4%) than in plasma samples from healthy human subjects (mean ± standard deviation, 55.9% ± 4.7%). Unbound plasma concentrations of polymyxin B were in the vicinity of or lower than the minimum inhibitory concentration of the pathogen. Conclusion. To our knowledge, this is the first study to report plasma concentrations over time and urinary recovery of polymyxin B in critically ill patients after intravenous administration. Polymyxin B is eliminated mainly by nonrenal pathways, and the total body clearance appears to be relatively insensitive to renal function. Additional investigations are required to assess the appropriateness of currently recommended doses of this drug for the treatment of severe infections in critically ill persons. © 2008 by the Infectious Diseases Society of America. All rights reserved.