Population Pharmacokinetics and Pharmacodynamics of Norvancomycin in Children With Malignant Hematological Disease

• Published in: Journal of clinical pharmacology Vol. 60; no. 9; p. 1220
• Main Authors: Wang, Jun, Li, Si-Chan, Ye, Qi, Gao, Liu-Liu, Nie, Ying-Ming, Xu, Hua, Wu, Mo, Cao, Peng, Wang, Yang
• Format: Journal Article
• Language: English
• Published: England 01.09.2020
• Subjects: norvancomycin; malignant hematological disease; children; pharmacodynamics; population pharmacokinetics
• ISSN: 1552-4604
• DOI: 10.1002/jcph.1618

Knowledge of pharmacokinetic (PK) behavior of norvancomycin (NVCM) in pediatric patients is lacking, which leads to empirical therapy in clinical practice. This study developed a population PK model of children aged 0-15 years; 112 opportunistic samples in total from 90 children were analyzed. The stability and prediction of the final model were evaluated by goodness-of-fit plots, nonparametric bootstrap, visual predictive check, and normalized prediction distribution errors. The PKs of NVCM in children was described by a 2-compartment model with first-order elimination along with body weight and estimated glomerular filtration rate as significant covariates on clearance. The population typical values of the PK parameters were as follows: clearance 0.12 L/kg/h, central compartment distribution volume 0.17 L/kg, peripheral compartment distribution volume 0.38 L/kg, and intercompartmental clearance 0.35 L/kg/h. Logistic analysis showed that the ratio of area under the concentration-time curve over 24 hours (AUC ) to minimum inhibitory concentration (MIC) had the strongest correlation with clinical efficacy, and at least 80% clinical efficiency could be achieved when AUC /MIC ≥ 221.06 was defined as the target. Monte Carlo simulation results suggested that a higher dose was required for this pediatric population in order to reach the target. The dosing regimen was optimized based on the final model. A population PK model of NVCM was first characterized in children with hematologic malignancy, and an evidence-based approach for NVCM dosage individualization was provided.