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Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis

The pharmacokinetic (PK) studies of meropenem in Chinese newborns with late-onset sepsis (LOS) are still lacking. Causative pathogens of LOS and their susceptibility patterns in China differ from the data abroad. We, therefore, conducted a developmental population pharmacokinetic–pharmacodynamic ana...

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Autores principales: Wu, Yue-E, Kou, Chen, Li, Xue, Tang, Bo-Hao, Yao, Bu-Fan, Hao, Guo-Xiang, Zheng, Yi, van den Anker, John, You, Dian-Ping, Shen, A-Dong, Zhao, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777159/
https://www.ncbi.nlm.nih.gov/pubmed/36553441
http://dx.doi.org/10.3390/children9121998
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author Wu, Yue-E
Kou, Chen
Li, Xue
Tang, Bo-Hao
Yao, Bu-Fan
Hao, Guo-Xiang
Zheng, Yi
van den Anker, John
You, Dian-Ping
Shen, A-Dong
Zhao, Wei
author_facet Wu, Yue-E
Kou, Chen
Li, Xue
Tang, Bo-Hao
Yao, Bu-Fan
Hao, Guo-Xiang
Zheng, Yi
van den Anker, John
You, Dian-Ping
Shen, A-Dong
Zhao, Wei
author_sort Wu, Yue-E
collection PubMed
description The pharmacokinetic (PK) studies of meropenem in Chinese newborns with late-onset sepsis (LOS) are still lacking. Causative pathogens of LOS and their susceptibility patterns in China differ from the data abroad. We, therefore, conducted a developmental population pharmacokinetic–pharmacodynamic analysis in Chinese newborns with the goal to optimize meropenem dosing regimens for LOS therapy. An opportunistic sampling strategy was used to collect meropenem samples, followed by model building and validation. A Monte Carlo simulation was performed to show the probability of target attainment (PTA) for various dosages. The information from 78 newborns (postmenstrual age: 27.4–46.1 weeks) was compiled and had a good fit to a 1-compartment model that had first order elimination. The median (range) values of estimated weight–normalized volume of distribution (V)and clearance (CL) were 0.60 (0.51–0.69) L/kg and 0.16 (0.04–0.51) L/h/kg, respectively. Covariate analysis revealed that postnatal age (PNA), gestational age (GA) and current weight (CW) were the most important factors in describing meropenem PK. Simulation results showed for LOS with a minimal inhibitory concentration (MIC) of 8 mg/L, the doses of 30 mg/kg 3 times daily (TID) as a 1-h infusion for newborns with GA ≤ 37 weeks and 40 mg/kg TID as a 3-h infusion for those with GA > 37 weeks were optimal, with PTA of 71.71% and 75.08%, respectively. In conclusion, we proposed an evidence-based dosing regimen of meropenem for LOS in Chinese newborns by using the population pharmacokinetic–pharmacodynamic analysis, based on domestic common pathogens and their susceptibility patterns.
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spelling pubmed-97771592022-12-23 Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis Wu, Yue-E Kou, Chen Li, Xue Tang, Bo-Hao Yao, Bu-Fan Hao, Guo-Xiang Zheng, Yi van den Anker, John You, Dian-Ping Shen, A-Dong Zhao, Wei Children (Basel) Brief Report The pharmacokinetic (PK) studies of meropenem in Chinese newborns with late-onset sepsis (LOS) are still lacking. Causative pathogens of LOS and their susceptibility patterns in China differ from the data abroad. We, therefore, conducted a developmental population pharmacokinetic–pharmacodynamic analysis in Chinese newborns with the goal to optimize meropenem dosing regimens for LOS therapy. An opportunistic sampling strategy was used to collect meropenem samples, followed by model building and validation. A Monte Carlo simulation was performed to show the probability of target attainment (PTA) for various dosages. The information from 78 newborns (postmenstrual age: 27.4–46.1 weeks) was compiled and had a good fit to a 1-compartment model that had first order elimination. The median (range) values of estimated weight–normalized volume of distribution (V)and clearance (CL) were 0.60 (0.51–0.69) L/kg and 0.16 (0.04–0.51) L/h/kg, respectively. Covariate analysis revealed that postnatal age (PNA), gestational age (GA) and current weight (CW) were the most important factors in describing meropenem PK. Simulation results showed for LOS with a minimal inhibitory concentration (MIC) of 8 mg/L, the doses of 30 mg/kg 3 times daily (TID) as a 1-h infusion for newborns with GA ≤ 37 weeks and 40 mg/kg TID as a 3-h infusion for those with GA > 37 weeks were optimal, with PTA of 71.71% and 75.08%, respectively. In conclusion, we proposed an evidence-based dosing regimen of meropenem for LOS in Chinese newborns by using the population pharmacokinetic–pharmacodynamic analysis, based on domestic common pathogens and their susceptibility patterns. MDPI 2022-12-19 /pmc/articles/PMC9777159/ /pubmed/36553441 http://dx.doi.org/10.3390/children9121998 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Wu, Yue-E
Kou, Chen
Li, Xue
Tang, Bo-Hao
Yao, Bu-Fan
Hao, Guo-Xiang
Zheng, Yi
van den Anker, John
You, Dian-Ping
Shen, A-Dong
Zhao, Wei
Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis
title Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis
title_full Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis
title_fullStr Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis
title_full_unstemmed Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis
title_short Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis
title_sort developmental population pharmacokinetics-pharmacodynamics of meropenem in chinese neonates and young infants: dosing recommendations for late-onset sepsis
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777159/
https://www.ncbi.nlm.nih.gov/pubmed/36553441
http://dx.doi.org/10.3390/children9121998
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