Population pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy
Standard
Population pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy. / Economou, Caleb J P; Kielstein, Jan T; Czock, David; Xie, Jiao; Field, Jonathan; Richards, Brent; Tallot, Mandy; Visser, Adam; Koenig, Christina; Hafer, Carsten; Schmidt, Julius J; Lipman, Jeffrey; Roberts, Jason A.
In: INT J ANTIMICROB AG, Vol. 52, No. 2, 08.2018, p. 151-157.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Population pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy
AU - Economou, Caleb J P
AU - Kielstein, Jan T
AU - Czock, David
AU - Xie, Jiao
AU - Field, Jonathan
AU - Richards, Brent
AU - Tallot, Mandy
AU - Visser, Adam
AU - Koenig, Christina
AU - Hafer, Carsten
AU - Schmidt, Julius J
AU - Lipman, Jeffrey
AU - Roberts, Jason A
N1 - Copyright © 2018. Published by Elsevier B.V.
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.ijantimicag.2018.03.001
DO - 10.1016/j.ijantimicag.2018.03.001
M3 - SCORING: Journal article
C2 - 29526606
VL - 52
SP - 151
EP - 157
JO - INT J ANTIMICROB AG
JF - INT J ANTIMICROB AG
SN - 0924-8579
IS - 2
ER -