Population pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy

Thumbnail Image
File version

Accepted Manuscript (AM)

Economou, Caleb JP
Kielstein, Jan T
Czock, David
Xie, Jiao
Field, Jonathan
Richards, Brent
Tallott, Mandy
Visser, Adam
Koenig, Christina
Hafer, Carsten
Schmidt, Julius J
Lipman, Jeffrey
Roberts, Jason A
Griffith University Author(s)
Primary Supervisor
Other Supervisors
File type(s)

Objectives: The 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. Methods: Critically 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. Results: Eleven 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. Conclusions: This 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.

Journal Title

International Journal of Antimicrobial Agents

Conference Title
Book Title




Thesis Type
Degree Program
Publisher link
Patent number
Grant identifier(s)
Rights Statement
Rights Statement

© 2018 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.

Item Access Status
Access the data
Related item(s)

Medical microbiology

Pharmacology and pharmaceutical sciences





Prolonged intermittent renal replacement therapy

Persistent link to this record

Economou, CJP; Kielstein, JT; Czock, D; Xie, J; Field, J; Richards, B; Tallott, M; Visser, A; Koenig, C; Hafer, C; Schmidt, JJ; Lipman, J; Roberts, JA, Population pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy, International Journal of Antimicrobial Agents, 2018, 52 (2), pp. 151-157