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

• Verfasst von: Economou, Caleb J. P. [VerfasserIn]
• Verfasst von: Czock, David [VerfasserIn]
• Titel: Population pharmacokinetics of vancomycin in critically ill patients receiving prolonged intermittent renal replacement therapy
• Verf.angabe: Caleb JP Economou, Jan T. Kielstein, David Czock, Jiao Xie, Jonathan Field, Brent Richards, Mandy Tallott, Adam Visser, Christina Koenig, Carsten Hafer, Julius J Schmidt, Jeffrey Lipman, Jason A Roberts
• Jahr: 2018
• Umfang: 7 S.
• Fussnoten: Gesehen am 19.05.2019
• Titel Quelle: Enthalten in: International journal of antimicrobial agents
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1991
• Jahr Quelle: 2018
• Band/Heft Quelle: 52(2018), 2, Seite 151-157
• ISSN Quelle: 1872-7913
• DOI: doi:10.1016/j.ijantimicag.2018.03.001
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Antibiotics
• Sach-SW: Dosing
• Sach-SW: Pharmacodynamics
• Sach-SW: Pharmacokinetics
• Sach-SW: Prolonged intermittent renal replacement therapy
• Sach-SW: Renal replacement therapy
• K10plus-PPN: 1669484637

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.