Population Pharmacokinetic Study of Vancomycin in Chinese Pediatric Patients with Hematological Malignancies

Abstract

STUDY OBJECTIVES Vancomycin is a primary antibiotic for the treatment of severe infections in children with malignant hematological disease. However, precise dosing of vancomycin is difficult in children because of high interindividual variability and limited data of pharmacokinetic profiles. The present study aims to develop a population pharmacokinetic (PPK) model for vancomycin in Chinese pediatric patients with hematological malignancies. DESIGN This was a retrospective pharmacokinetic study. SETTING The setting for this study was a tertiary-care children's hospital. PATIENTS This study included 92 pediatric patients with hematological malignancies who received vancomycin and experienced therapeutic drug monitoring from February 2017 to December 2018. MEASUREMENTS AND MAIN RESULTS A PPK model was generated with a nonlinear mixed effects model. In addition, required doses to achieve target therapeutic concentrations were simulated based on the final model. A one-compartment model with first-order elimination fit the concentration data best. Actual body weight (BW) and glomerular filtration rate (GFR) were the significant influential factors on the clearance (CL) of vancomycin. The final PPK model for CL was CL (L/h) = 4.18 Â GFR=145 ð Þ 0:741 Â BW=25 ð Þ K , K = BW À0:856 ð Þ = BW À0:856 þ 6:53 À0:856 ð Þ , and the volume of distribution was 22.3 L. The model proved to be robust and reliable. Reference dosing regimens were proposed based on the final model. CONCLUSIONS A PPK model of vancomycin was established for Chinese pediatric patients with hematological malignancies using a nonlinear mixed effects model, which provided a reference for the clinical application of vancomycin. KEY WORDS vancomycin, pediatrics, hematological malignancies, population pharmacokinetics.

Implementation of Vancomycin Therapeutic Monitoring Guidelines: Focus on Bayesian Estimation Tools in Neonatal and Pediatric Patients

“…18,23,34 Three studies identified weight and GFR as primary covariates, although GFR incorporates SCr. 19,20,22 PMA was a significant covariate in 2 studies by Moffett et al, which assessed cardiac surgery and extracorporeal membrane oxygenation patients, although several study patients were neonates. 33,35 Eight studies used the Jaffe SCr assay 18,19,23-25,34,36 methods, and 3 studies used enzymatic methods.…”

“…Various subpopulations were explored, including patients with obesity, renal failure, cystic fibrosis, and hematological malignancies. [18][19][20][21][22] All models identified age, body weight, or SCr as significant covariates for vancomycin CL. Among the covariates, SCr appeared to be a crucial component that impacted vancomycin CL in 13 studies.…”

Individualized Delivery of Vancomycin by Model-Informed Bayesian Dosing Approach to Maintain an <i>AUC</i>_<i>24</i> Target in Critically Ill Patients

“…Validated population pharmacokinetic (PPK) models facilitate the design of initial dose regimens of vancomycin, and Bayesian estimation can be used to guide dose adjustment following TDM [9]. Although there have been many reports for PPK models of vancomycin [10][11][12][13], the data for Chinese ICU patients have rarely been reported. The objectives of this study were to construct a PPK model to describe the PK characteristics of vancomycin and to evaluate the Bayesian-guided vancomycin dosing in ICU patients.…”