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

作者：Economou Caleb J P; 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^*

来源：International Journal of Antimicrobial Agents, 2018, 52(2): 151-157.

DOI：10.1016/j.ijantimicag.2018.03.001

• Antibiotics
• Dosing
• Pharmacokinetics
• Pharmacodynamics
• Renal replacement therapy
• Prolonged intermittent renal replacement therapy

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 (R). The target vancomycin exposures were the area under the concentration-time curve within a 24-h period (AUC(0-24))/minimum inhibitory concentration (MIC) ratio of 400 for efficacy and AUC(0-24) 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/m(2), 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.

• 出版日期2018-8