Abstract
The pharmacokinetics of vancomycin vary among neonates, and we aimed to conduct population pharmacokinetic analysis to determine the optimal dosage of vancomycin in Korean neonates. From a retrospective chart review, neonates treated with vancomycin from 2008 to 2017 in a neonatal intensive care unit (NICU) were included. Vancomycin concentrations were collected based on therapeutic drug monitoring, and other patient characteristics were gathered through electronic medical records. We applied nonlinear mixed-effect modeling to build the population pharmacokinetic model. One- and two-compartment models with first-order elimination were evaluated as potential structural pharmacokinetic models. Allometric and isometric scaling was applied to standardize pharmacokinetic parameters for clearance and volume of distribution, respectively, using fixed powers (0.75 and 1, respectively, for clearance and volume). The predictive performance of the final model was developed, and dosing strategies were explored using Monte Carlo simulations with AUC0–24 targets 400–600. The patient cohort included 207 neonates, and 900 vancomycin concentrations were analyzed. Only 37.4% of the analyzed concentrations were within trough concentrations 5–15 µg/mL. A one-compartment model with first-order elimination best described the vancomycin pharmacokinetics in neonates. Postmenstrual age (PMA) and creatinine clearance (CLcr) affected the clearance of vancomycin, and model evaluation confirmed the robustness of the final model. Population pharmacokinetic modeling and dose optimization of vancomycin in Korean neonates showed that vancomycin clearance was related to PMA and CLcr, as well as body weight. A higher dosage regimen than the typical recommendation is suggested.
Highlights
Pharmaceutical Medicine and Regulatory Science, Yonsei University, Veritas Hall D #214, Yonsei University International Campus, Songdogwahak‐ro 85, Yeonsu‐gu, Incheon, Korea. 4These authors contributed : Soon
Vancomycin treatment was administered at a median post-natal age (PNA) of 2.3 weeks and postmenstrual age (PMA) of 35.6 weeks
Our results were similar to those in previous studies showing that PMA and renal function are related to vancomycin PK parameters in neonates[12,13,16,17]
Summary
Pharmaceutical Medicine and Regulatory Science, Yonsei University, Veritas Hall D #214, Yonsei University International Campus, Songdogwahak‐ro 85, Yeonsu‐gu, Incheon, Korea. 4These authors contributed : Soon. Pharmaceutical Medicine and Regulatory Science, Yonsei University, Veritas Hall D #214, Yonsei University International Campus, Songdogwahak‐ro 85, Yeonsu‐gu, Incheon, Korea. Several population pharmacokinetic models of vancomycin exist, only a few individualized, modelbased dosing algorithms in neonates are a vailable[9,12,13]. Population PK modeling and simulation approaches allow us to characterize population averages, to assess the inter- and intra-subject variability of pharmacokinetic parameters, and to identify the optimal dosing of antibiotics. This study aimed to conduct a population pharmacokinetic analysis to obtain pharmacokinetic data for vancomycin in Korean neonate infants and to develop an optimal vancomycin dosing strategy using model simulation
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