Pharmacokinetics of polymyxin B1 in patients with multidrug-resistant Gram-negative bacterial infections

Polymyxin B is increasingly used clinically for the treatment of multidrug-resistant Gram-negative infections, despite very limited understanding of its disposition in humans. The disposition of intravenous polymyxin B1 in 9 adult patients was characterized. Random blood samples (specifically timed in relation to the dose administered) were obtained, and the serum concentrations of polymyxin B1 were assayed using a validated methodology by liquid chromatography mass spectroscopy. The serum concentration profiles of all the patients were analyzed by a population pharmacokinetic analysis using the nonparametric adaptive grid program, The mean volume of distribution and elimination half-life were found to be 47.2 L and 13.6 h, respectively. This is the 1st case series to date in which the pharmacokinetics of polymyxin B1 after intravenous administration are described. The results of the series in conjunction with pharmacodynamic and susceptibility surveillance studies could facilitate an approach to the design of optimal dosing regimens. (C) 2008 Elsevier Inc. All rights reserved.