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中国正常及肾功能增强婴儿万古霉素的群体药代动力学建模

Population Pharmacokinetics Modeling of Vancomycin Among Chinese Infants With Normal and Augmented Renal Function.

作者信息

Li De-Yi, Li Ling, Li Gui-Zhou, Hu Ya-Hui, Guo Hong-Li, Jing Xia, Chen Feng, Ji Xing, Xu Jing, Dai Hao-Ran

机构信息

Pharmaceutical Sciences Research Center, Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China.

School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.

出版信息

Front Pediatr. 2021 Sep 20;9:713588. doi: 10.3389/fped.2021.713588. eCollection 2021.

Abstract

There have been good amounts of population pharmacokinetics (PPK) models of vancomycin for Chinese pediatric patients, but none of them had a special focus on modeling infant population with different levels of renal function. Since renal function variability is prominent among infant population and the clearance (CL) of vancomycin is heavily related to renal excretion, it is important to establish precise PPK models based on individual renal function levels. We employed a PPK approach to develop three models of vancomycin in parallel for Chinese pediatric patients with normal renal function [estimated glomerular filtration rate (eGFR) between 30 and 86 ml/min/1.73 m, Model 1], with augmented renal function (eGFR ≥ 86 ml/min/1.73 m, Model 2), or with all levels of renal function (Model 3). Three one-compartment models with first-order elimination kinetics were established. The predictive ability of Model 1 and Model 2 among each certain population is comparable with that of Model 3 with no statistical difference. Our study revealed that among the infant population with augmented renal function, only body weight was included as a covariate, which indicated that for an infant whose eGFR ≥ 86 ml/min/1.73 m, taking blood sample is not compulsory for predicting vancomycin blood concentration, which avoids unnecessary injury to vulnerable infants.

摘要

已有不少针对中国儿科患者的万古霉素群体药代动力学(PPK)模型,但均未特别关注对不同肾功能水平婴儿群体的建模。由于婴儿群体中肾功能变异性显著,且万古霉素的清除率(CL)与肾脏排泄密切相关,因此基于个体肾功能水平建立精确的PPK模型很重要。我们采用PPK方法,为中国肾功能正常[估计肾小球滤过率(eGFR)在30至86 ml/min/1.73 m之间,模型1]、肾功能增强(eGFR≥86 ml/min/1.73 m,模型2)或所有肾功能水平(模型3)的儿科患者并行开发了三个万古霉素模型。建立了三个具有一级消除动力学的单室模型。模型1和模型2在各特定群体中的预测能力与模型3相当,无统计学差异。我们的研究表明,在肾功能增强的婴儿群体中,仅将体重作为协变量,这表明对于eGFR≥86 ml/min/1.73 m的婴儿,预测万古霉素血药浓度时无需采集血样,避免了对脆弱婴儿造成不必要的伤害。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728d/8489377/fd948dafceb0/fped-09-713588-g0001.jpg

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