• Economou Caleb J P CJP University of Queensland Centre for Clinical Research, Faculty of Medicine, Australia; ICON Cancer Foundation, Department of Research, Brisbane, Qu, Jan T Kielstein, David Czock, Jiao Xie, Jonathan Field, Brent Richards, Mandy Tallott, Adam Visser, Christina Koenig, Carsten Hafer, Julius J Schmidt, Jeffrey Lipman, and Jason A Roberts.
• University of Queensland Centre for Clinical Research, Faculty of Medicine, Australia; ICON Cancer Foundation, Department of Research, Brisbane, Queensland, Australia.
• Int. J. Antimicrob. Agents. 2018 Aug 1; 52 (2): 151-157.

ObjectivesThe aim of this study was to describe the population pharmacokinetics of vancomycin during prolonged intermittent renal replacement therapy (PIRRT) in critically ill patients with acute kidney injury.MethodsCritically ill patients prescribed vancomycin across two sites had blood samples collected during one to three dosing intervals during which PIRRT was performed. Plasma samples were assayed with a validated immunoassay method. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Pmetrics®. The target vancomycin exposures were the area under the concentration-time curve within a 24-h period (AUC0-24)/minimum inhibitory concentration (MIC) ratio of 400 for efficacy and AUC0-24 700 for toxicity.ResultsEleven critically ill patients (seven male) were enrolled and contributed 192 plasma samples. The patient's mean ± standard deviation (SD) age, weight and body mass index (BMI) were 57 ± 13 years, 98 ± 43 kg and 31 ± 9 kg/m2, respectively. A two-compartment linear model adequately described the data. The mean ± SD population pharmacokinetic parameter estimates were PIRRT clearance (CL) 3.47 ± 1.99 L/h, non-PIRRT CL 2.15 ± 2.07 L/h, volume of distribution of the central compartment (Vc) 41.85 ± 24.33 L, distribution rate constant from central to peripheral compartment 5.97 ± 7.93 per h and from peripheral to central compartment 5.29 ± 6.65 per h. Assuming a MIC of 1 mg/L, vancomycin doses of 25 mg/kg per day are suggested to be efficacious, whilst minimising toxic, exposures.ConclusionsThis is the first population pharmacokinetic study of vancomycin in patients receiving PIRRT and we observed large pharmacokinetic variability. Empirically, weight-based doses that are appropriate for the duration of PIRRT, should be selected and supplemented with therapeutic drug monitoring.Copyright © 2018 Elsevier Ltd. All rights reserved.

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