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Optimal dose of cefotaxime in neonates with early-onset sepsis: A developmental pharmacokinetic model-based evaluation

Objective: The perspective of real-world study is especially relevant to newborns, enabling dosage regimen optimization and regulatory approval of medications for use in newborns. The aim of the present study was to conduct a pharmacokinetic analysis of cefotaxime and evaluate the dosage used in new...

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Autores principales: Shang, Zhen-Hai, Wu, Yue-E, Lv, Dong-Mei, Zhang, Wei, Liu, Wen-Qiang, van den Anker, John, Xu, Yan, Zhao, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490083/
https://www.ncbi.nlm.nih.gov/pubmed/36160425
http://dx.doi.org/10.3389/fphar.2022.916253
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author Shang, Zhen-Hai
Wu, Yue-E
Lv, Dong-Mei
Zhang, Wei
Liu, Wen-Qiang
van den Anker, John
Xu, Yan
Zhao, Wei
author_facet Shang, Zhen-Hai
Wu, Yue-E
Lv, Dong-Mei
Zhang, Wei
Liu, Wen-Qiang
van den Anker, John
Xu, Yan
Zhao, Wei
author_sort Shang, Zhen-Hai
collection PubMed
description Objective: The perspective of real-world study is especially relevant to newborns, enabling dosage regimen optimization and regulatory approval of medications for use in newborns. The aim of the present study was to conduct a pharmacokinetic analysis of cefotaxime and evaluate the dosage used in newborns with early-onset sepsis (EOS) using real-world data in order to support the rational use in the clinical practice. Methods: This prospective, open-label study was performed in newborns with EOS. A developmental pharmacokinetic-pharmacodynamic model of cefotaxime in EOS patients was established based on an opportunistic sampling method. Then, clinical evaluation of cefotaxime was conducted in newborns with EOS using real-world data. Results: A one-compartment model with first-order elimination was developed, using 101 cefotaxime concentrations derived from 51 neonates (30.1–41.3°C weeks postmenstrual age), combining current weight and postnatal age. The pharmacokinetic-pharmacodynamic target was defined as the free cefotaxime concentration above MIC during 70% of the dosing interval (70% fT > MIC), and 100% of neonates receiving the dose of 50 mg/kg, BID attained the target evaluated using the model. Additionally, only two newborns had adverse reactions possibly related to cefotaxime treatment, including diarrhea and feeding intolerance. Conclusion: This prospective real-world study demonstrated that cefotaxime (50 mg/kg, BID) had a favorable efficacy and an accepted safety profile for neonates with EOS.
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spelling pubmed-94900832022-09-22 Optimal dose of cefotaxime in neonates with early-onset sepsis: A developmental pharmacokinetic model-based evaluation Shang, Zhen-Hai Wu, Yue-E Lv, Dong-Mei Zhang, Wei Liu, Wen-Qiang van den Anker, John Xu, Yan Zhao, Wei Front Pharmacol Pharmacology Objective: The perspective of real-world study is especially relevant to newborns, enabling dosage regimen optimization and regulatory approval of medications for use in newborns. The aim of the present study was to conduct a pharmacokinetic analysis of cefotaxime and evaluate the dosage used in newborns with early-onset sepsis (EOS) using real-world data in order to support the rational use in the clinical practice. Methods: This prospective, open-label study was performed in newborns with EOS. A developmental pharmacokinetic-pharmacodynamic model of cefotaxime in EOS patients was established based on an opportunistic sampling method. Then, clinical evaluation of cefotaxime was conducted in newborns with EOS using real-world data. Results: A one-compartment model with first-order elimination was developed, using 101 cefotaxime concentrations derived from 51 neonates (30.1–41.3°C weeks postmenstrual age), combining current weight and postnatal age. The pharmacokinetic-pharmacodynamic target was defined as the free cefotaxime concentration above MIC during 70% of the dosing interval (70% fT > MIC), and 100% of neonates receiving the dose of 50 mg/kg, BID attained the target evaluated using the model. Additionally, only two newborns had adverse reactions possibly related to cefotaxime treatment, including diarrhea and feeding intolerance. Conclusion: This prospective real-world study demonstrated that cefotaxime (50 mg/kg, BID) had a favorable efficacy and an accepted safety profile for neonates with EOS. Frontiers Media S.A. 2022-09-07 /pmc/articles/PMC9490083/ /pubmed/36160425 http://dx.doi.org/10.3389/fphar.2022.916253 Text en Copyright © 2022 Shang, Wu, Lv, Zhang, Liu, van den Anker, Xu and Zhao. https://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(s) 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
Shang, Zhen-Hai
Wu, Yue-E
Lv, Dong-Mei
Zhang, Wei
Liu, Wen-Qiang
van den Anker, John
Xu, Yan
Zhao, Wei
Optimal dose of cefotaxime in neonates with early-onset sepsis: A developmental pharmacokinetic model-based evaluation
title Optimal dose of cefotaxime in neonates with early-onset sepsis: A developmental pharmacokinetic model-based evaluation
title_full Optimal dose of cefotaxime in neonates with early-onset sepsis: A developmental pharmacokinetic model-based evaluation
title_fullStr Optimal dose of cefotaxime in neonates with early-onset sepsis: A developmental pharmacokinetic model-based evaluation
title_full_unstemmed Optimal dose of cefotaxime in neonates with early-onset sepsis: A developmental pharmacokinetic model-based evaluation
title_short Optimal dose of cefotaxime in neonates with early-onset sepsis: A developmental pharmacokinetic model-based evaluation
title_sort optimal dose of cefotaxime in neonates with early-onset sepsis: a developmental pharmacokinetic model-based evaluation
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490083/
https://www.ncbi.nlm.nih.gov/pubmed/36160425
http://dx.doi.org/10.3389/fphar.2022.916253
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