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Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations

The main goal of our study was to characterize the population pharmacokinetics of vancomycin in critically ill Chinese neonates to develop a pharmacokinetic model and investigate factors that have significant influences on the pharmacokinetics of vancomycin in this population. The study population c...

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Autores principales: Li, Zhi-ling, Liu, Yi-xi, Jiao, Zheng, Qiu, Gang, Huang, Jian-quan, Xiao, Yu-bo, Wu, Shu-jin, Wang, Chen-yu, Hu, Wen-juan, Sun, Hua-jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029141/
https://www.ncbi.nlm.nih.gov/pubmed/29997498
http://dx.doi.org/10.3389/fphar.2018.00603
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author Li, Zhi-ling
Liu, Yi-xi
Jiao, Zheng
Qiu, Gang
Huang, Jian-quan
Xiao, Yu-bo
Wu, Shu-jin
Wang, Chen-yu
Hu, Wen-juan
Sun, Hua-jun
author_facet Li, Zhi-ling
Liu, Yi-xi
Jiao, Zheng
Qiu, Gang
Huang, Jian-quan
Xiao, Yu-bo
Wu, Shu-jin
Wang, Chen-yu
Hu, Wen-juan
Sun, Hua-jun
author_sort Li, Zhi-ling
collection PubMed
description The main goal of our study was to characterize the population pharmacokinetics of vancomycin in critically ill Chinese neonates to develop a pharmacokinetic model and investigate factors that have significant influences on the pharmacokinetics of vancomycin in this population. The study population consisted of 80 neonates in the neonatal intensive care unit (ICU) from which 165 trough and peak concentrations of vancomycin were obtained. Nonlinear mixed effect modeling was used to develop a population pharmacokinetic model for vancomycin. The stability and predictive ability of the final model were evaluated based on diagnostic plots, normalized prediction distribution errors and the bootstrap method. Serum creatinine (Scr) and body weight were significant covariates on the clearance of vancomycin. The average clearance was 0.309 L/h for a neonate with Scr of 23.3 μmol/L and body weight of 2.9 kg. No obvious ethnic differences in the clearance of vancomycin were found relative to the earlier studies of Caucasian neonates. Moreover, the established model indicated that in patients with a greater renal clearance status, especially Scr < 15 μmol/L, current guideline recommendations would likely not achieve therapeutic area under the concentration-time curve over 24 h/minimum inhibitory concentration (AUC(24h)/MIC) ≥ 400. The exceptions to this are British National Formulary (2016–2017), Blue Book (2016) and Neofax (2017). Recommended dose regimens for neonates with different Scr levels and postmenstrual ages were estimated based on Monte Carlo simulations and the established model. These findings will be valuable for developing individualized dosage regimens in the neonatal ICU setting.
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spelling pubmed-60291412018-07-11 Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations Li, Zhi-ling Liu, Yi-xi Jiao, Zheng Qiu, Gang Huang, Jian-quan Xiao, Yu-bo Wu, Shu-jin Wang, Chen-yu Hu, Wen-juan Sun, Hua-jun Front Pharmacol Pharmacology The main goal of our study was to characterize the population pharmacokinetics of vancomycin in critically ill Chinese neonates to develop a pharmacokinetic model and investigate factors that have significant influences on the pharmacokinetics of vancomycin in this population. The study population consisted of 80 neonates in the neonatal intensive care unit (ICU) from which 165 trough and peak concentrations of vancomycin were obtained. Nonlinear mixed effect modeling was used to develop a population pharmacokinetic model for vancomycin. The stability and predictive ability of the final model were evaluated based on diagnostic plots, normalized prediction distribution errors and the bootstrap method. Serum creatinine (Scr) and body weight were significant covariates on the clearance of vancomycin. The average clearance was 0.309 L/h for a neonate with Scr of 23.3 μmol/L and body weight of 2.9 kg. No obvious ethnic differences in the clearance of vancomycin were found relative to the earlier studies of Caucasian neonates. Moreover, the established model indicated that in patients with a greater renal clearance status, especially Scr < 15 μmol/L, current guideline recommendations would likely not achieve therapeutic area under the concentration-time curve over 24 h/minimum inhibitory concentration (AUC(24h)/MIC) ≥ 400. The exceptions to this are British National Formulary (2016–2017), Blue Book (2016) and Neofax (2017). Recommended dose regimens for neonates with different Scr levels and postmenstrual ages were estimated based on Monte Carlo simulations and the established model. These findings will be valuable for developing individualized dosage regimens in the neonatal ICU setting. Frontiers Media S.A. 2018-06-26 /pmc/articles/PMC6029141/ /pubmed/29997498 http://dx.doi.org/10.3389/fphar.2018.00603 Text en Copyright © 2018 Li, Liu, Jiao, Qiu, Huang, Xiao, Wu, Wang, Hu and Sun. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Zhi-ling
Liu, Yi-xi
Jiao, Zheng
Qiu, Gang
Huang, Jian-quan
Xiao, Yu-bo
Wu, Shu-jin
Wang, Chen-yu
Hu, Wen-juan
Sun, Hua-jun
Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations
title Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations
title_full Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations
title_fullStr Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations
title_full_unstemmed Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations
title_short Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations
title_sort population pharmacokinetics of vancomycin in chinese icu neonates: initial dosage recommendations
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029141/
https://www.ncbi.nlm.nih.gov/pubmed/29997498
http://dx.doi.org/10.3389/fphar.2018.00603
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