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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Population pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy
International Journal of Antimicrobial Agents, Volume 52, No. 2, Year 2018
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Description
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. © 2018 Elsevier Ltd
Authors & Co-Authors
Kielstein, Jan Thomas
Unknown Affiliation
Czock, David
Germany, Heidelberg
Universitätsklinikum Heidelberg
Xie, Jiao
Australia, Brisbane
The University of Queensland
Field, Jonathan
Australia, Southport
Gold Coast University Hospital
Richards, Brent
Australia, Southport
Gold Coast University Hospital
Tallott, Mandy
Australia, Southport
Gold Coast University Hospital
Schmidt, Julius J.
Germany, Hannover
Hannover Medical School
Lipman, Jeffrey
Australia, Brisbane
The University of Queensland
Australia, Brisbane
Royal Brisbane and Women's Hospital
Roberts, Jason A.
Australia, Brisbane
The University of Queensland
Australia, Brisbane
Royal Brisbane and Women's Hospital
Statistics
Citations: 21
Authors: 9
Affiliations: 6
Identifiers
Doi:
10.1016/j.ijantimicag.2018.03.001
ISSN:
09248579
Research Areas
Environmental
Health System And Policy
Violence And Injury
Study Design
Cross Sectional Study
Participants Gender
Male