Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units

Abstract Management of vancomycin administration for intensive care units (ICU) patients remains a challenge. The aim of this study was to describe a population pharmacokinetic model of vancomycin for optimizing the dose regimen for ICU patients. We prospectively enrolled 466 vancomycin-treated pati...

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Autores principales:	Zhong Lin, Dan-yang Chen, Yan-Wu Zhu, Zheng-li Jiang, Ke Cui, Sheng Zhang, Li-hua Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eee1824b30bf445981590749a628890a
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spelling	oai:doaj.org-article:eee1824b30bf445981590749a628890a2021-12-02T14:16:06ZPopulation pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units10.1038/s41598-021-82312-22045-2322https://doaj.org/article/eee1824b30bf445981590749a628890a2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82312-2https://doaj.org/toc/2045-2322Abstract Management of vancomycin administration for intensive care units (ICU) patients remains a challenge. The aim of this study was to describe a population pharmacokinetic model of vancomycin for optimizing the dose regimen for ICU patients. We prospectively enrolled 466 vancomycin-treated patients hospitalized in the ICU, collected trough or approach peak blood samples of vancomycin and recorded corresponding clinical information from July 2015 to December 2017 at Tai Zhou Hospital of Zhejiang Province. The pharmacokinetics of vancomycin was analyzed by nonlinear mixed effects modeling with Kinetica software. Internal and external validation was evaluated by the maximum likelihood method. Then, the individual dosing regimens of the 92 patients hospitalized in the ICU whose steady state trough concentrations exceeded the target range (10–20 μg/ml) were adjusted by the Bayes feedback method. The final population pharmacokinetic model show that clearance rate (CL) of vancomycin will be raised under the conditions of dopamine combined treatment, severe burn status (Burn-S) and increased total body weight (TBW), but reduced under the conditions of increased serum creatinine (Cr) and continuous renal replacement therapy status; Meanwhile, the apparent distribution volume (V) of vancomycin will be enhanced under the terms of increased TBW, however decreased under the terms of increased age and Cr. The population pharmacokinetic parameters (CL and V) according to the final model were 3.16 (95%CI 2.83, 3.40) L/h and 60.71 (95%CI 53.15, 67.46). The mean absolute prediction error for external validation by the final model was 12.61% (95CI 8.77%, 16.45%). Finally, the prediction accuracy of 90.21% of the patients’ detected trough concentrations that were distributed in the target range of 10–20 μg/ml after dosing adjustment was found to be adequate. There is significant heterogeneity in the CL and V of vancomycin in ICU patients. The constructed model is sufficiently precise for the Bayesian dose prediction of vancomycin concentrations for the population of ICU Chinese patients.Zhong LinDan-yang ChenYan-Wu ZhuZheng-li JiangKe CuiSheng ZhangLi-hua ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhong Lin Dan-yang Chen Yan-Wu Zhu Zheng-li Jiang Ke Cui Sheng Zhang Li-hua Chen Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units
description	Abstract Management of vancomycin administration for intensive care units (ICU) patients remains a challenge. The aim of this study was to describe a population pharmacokinetic model of vancomycin for optimizing the dose regimen for ICU patients. We prospectively enrolled 466 vancomycin-treated patients hospitalized in the ICU, collected trough or approach peak blood samples of vancomycin and recorded corresponding clinical information from July 2015 to December 2017 at Tai Zhou Hospital of Zhejiang Province. The pharmacokinetics of vancomycin was analyzed by nonlinear mixed effects modeling with Kinetica software. Internal and external validation was evaluated by the maximum likelihood method. Then, the individual dosing regimens of the 92 patients hospitalized in the ICU whose steady state trough concentrations exceeded the target range (10–20 μg/ml) were adjusted by the Bayes feedback method. The final population pharmacokinetic model show that clearance rate (CL) of vancomycin will be raised under the conditions of dopamine combined treatment, severe burn status (Burn-S) and increased total body weight (TBW), but reduced under the conditions of increased serum creatinine (Cr) and continuous renal replacement therapy status; Meanwhile, the apparent distribution volume (V) of vancomycin will be enhanced under the terms of increased TBW, however decreased under the terms of increased age and Cr. The population pharmacokinetic parameters (CL and V) according to the final model were 3.16 (95%CI 2.83, 3.40) L/h and 60.71 (95%CI 53.15, 67.46). The mean absolute prediction error for external validation by the final model was 12.61% (95CI 8.77%, 16.45%). Finally, the prediction accuracy of 90.21% of the patients’ detected trough concentrations that were distributed in the target range of 10–20 μg/ml after dosing adjustment was found to be adequate. There is significant heterogeneity in the CL and V of vancomycin in ICU patients. The constructed model is sufficiently precise for the Bayesian dose prediction of vancomycin concentrations for the population of ICU Chinese patients.
format	article
author	Zhong Lin Dan-yang Chen Yan-Wu Zhu Zheng-li Jiang Ke Cui Sheng Zhang Li-hua Chen
author_facet	Zhong Lin Dan-yang Chen Yan-Wu Zhu Zheng-li Jiang Ke Cui Sheng Zhang Li-hua Chen
author_sort	Zhong Lin
title	Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units
title_short	Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units
title_full	Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units
title_fullStr	Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units
title_full_unstemmed	Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units
title_sort	population pharmacokinetic modeling and clinical application of vancomycin in chinese patients hospitalized in intensive care units
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/eee1824b30bf445981590749a628890a
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Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units

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