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

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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
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2018
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Abstract

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.

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International Journal of Antimicrobial Agents

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52

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2

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© 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.

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Medical microbiology

Pharmacology and pharmaceutical sciences

Antibiotics

Dosing

Pharmacodynamics

Pharmacokinetics

Prolonged intermittent renal replacement therapy

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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

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