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. 2024 Nov 15;26(11):1162-1168.
doi: 10.7499/j.issn.1008-8830.2406078.

[Establishment of a population pharmacokinetic model for linezolid in neonates with sepsis]

[Article in Chinese]
Zong-Tai Feng  1 , Lian Tang, Zu-Ming Yang  1 , Chu-Chu Gao  1 , Jia-Hui Li, Yan Cai  1 , Lu-Fen Duan
Affiliations

[Establishment of a population pharmacokinetic model for linezolid in neonates with sepsis]

[Article in Chinese]
Zong-Tai Feng et al. Zhongguo Dang Dai Er Ke Za Zhi. .

Abstract
in English, Chinese

Objectives: To establish the pharmacokinetic model of linezolid in neonates, and to optimize the administration regimen.

Methods: A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy, and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected, and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features.

Results: The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination, and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h, respectively. The results of goodness of fit, visualization verification, and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows: 6 mg/kg, q8h, at 28 weeks of gestational age (GA); 8 mg/kg, q8h, at 32 weeks of GA; 9 mg/kg, q8h, at 34-37 weeks of GA; 11 mg/kg, q8h, at 40 weeks of GA.

Conclusions: The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

目的: 建立利奈唑胺在新生儿中的药动学模型并优化给药方案。方法: 前瞻性收集64例使用利奈唑胺抗感染治疗的败血症新生儿为研究对象，采用液相色谱串联质谱法检测血药浓度，收集临床资料，采用非线性混合效应建模法建立群体药动学（population pharmacokinetic, PPK）模型，采用蒙特卡洛模拟和评价不同特征患儿的最佳给药方案。结果: 利奈唑胺在新生儿体内的药动学特性可用一个具有一级消除的单室模型来描述，表观分布容积和清除率的群体典型值分别为0.79 L和0.34 L/h。拟合优度、可视化验证及自举法结果表明，模型稳健，参数估算及预测结果可靠。蒙特卡洛模拟显示新生儿利奈唑胺最佳给药方案，胎龄（gestational age, GA）28周6 mg/kg，q8h；GA 32周8 mg/kg，q8h；GA 34~37周9 mg/kg，q8h；GA 40周11 mg/kg，q8h。结论: 该研究建立的PPK模型可为新生儿利奈唑胺的个体化给药提供参考，GA和用药时体重是影响新生儿利奈唑胺清除率的显著性因素。.

Keywords: Linezolid; Monte Carlo simulation; Neonate; Population pharmacokinetics; Sepsis; Therapeutic drug monitoring.

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Conflict of interest statement

所有作者均声明不存在利益冲突。

Figures

图1
图1. 利奈唑胺血药浓度-时间散点图 横坐标为距离末次给药后时间，纵坐标为利奈唑胺血药浓度。
图2
图2. 基础模型（A和C）和最终模型（B和D）拟合优度图 A为基础模型实测值-个体预测值的散点图；B为最终模型实测值-个体预测值的散点图；C为基础模型实测值-群体预测值的散点图；D为最终模型实测值-群体预测值的散点图。
图3
图3. 基础模型（A和C）和最终模型（B和D）权重残差散点图 A为基础模型条件加权残差-群体预测值的散点图；B为最终模型条件加权残差-群体预测值的散点图；C为基础模型条件加权残差-给药后时间的散点图；D为最终模型条件加权残差-给药后时间的散点图。上下两条红色曲线分别为条件权重残差上下半区趋势线，中间蓝色曲线为整体趋势线。
See this image and copyright information in PMC

References

    1. Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis[J]. Lancet, 2017, 390(10104): 1770-1780. DOI: 10.1016/S0140-6736(17)31002-4. - DOI - PubMed
    1. 中华医学会儿科学分会新生儿学组, 中国医师协会新生儿科医师分会感染专业委员会 . 新生儿败血症诊断及治疗专家共识（2019年版）[J]. 中华儿科杂志, 2019, 57(4): 252-257. DOI: 10.3760/cma.j.issn.0578-1310.2019.04.005. - DOI - PubMed
    1. Nelson JD, Bradley JS, Kimberlin DW, et al. . 2021 Nelsons Pediatric Antimicrobial Therapy[M]. 27th ed. Itasca: American Academy of Pediatrics, 2021.
    1. Liu P, Capitano B, Stein A, et al. . Clinical outcomes of linezolid and vancomycin in patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus stratified by baseline renal function: a retrospective, cohort analysis[J]. BMC Nephrol, 2017, 18(1): 168. DOI: 10.1186/s12882-017-0581-y. - DOI - PMC - PubMed
    1. Kocher S, Müller W, Resch B. Linezolid treatment of nosocomial bacterial infection with multiresistant Gram-positive pathogens in preterm infants: a systematic review[J]. Int J Antimicrob Agents, 2010, 36(2): 106-110. DOI: 10.1016/j.ijantimicag.2010.03.030. - DOI - PubMed

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