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中国新生儿和小婴儿万古霉素个体化给药方案的群体药代动力学模型

A population pharmacokinetic model for individualised dosage regimens of vancomycin in Chinese neonates and young infants.

作者信息

Song Lin, He Cui-Yao, Yin Nan-Ge, Liu Fang, Jia Yun-Tao, Liu Yao

机构信息

Department of Pharmacy, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.

Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.

出版信息

Oncotarget. 2017 Oct 26;8(62):105211-105221. doi: 10.18632/oncotarget.22114. eCollection 2017 Dec 1.

Abstract

Population pharmacokinetic (PPK) modelling is an easy and impartment method for estimating drug concentration for use inindividualized therapy, especially for young patients and to help protect drug-induced diseases. The purpose of this study was to develop a PPK model for effective dosing of vancomycin in Chinese neonates and young infants. The PPK modelling tool Phoenix NLME was use to assess demographic and routine clinical pharmacokinetic (PK) data retrospectively collected for patients admitted to Children's Hospital of Chongqing Medical University between 2011 and 2016. Data of patients admitted to the hospital between January and June of 2017 were used in validation study, and the final model was also preliminary validated in 2 cases in another hospital. A total of 421 serum samples from 316 patients were included in the initial PPK analysis. A two-compartment PPK model was developed, and exponential-error model was used to describe inter-individual variability of clearance. Residual variability was described by an additive model. The final PPK model was demonstrated as valid by internal and external model evaluation. Of note, the clearance and volume of vancomycin in Chinese neonates and young infants may be greater than in Caucasians. Herein, we describe the establishment of an accurate PPK model of vancomycin for Chinese neonates and young infants, which may be useful as a dosing algorithm for this particular paediatric population.

摘要

群体药代动力学(PPK)建模是一种简便且客观的方法,用于估算药物浓度以用于个体化治疗,尤其适用于年轻患者,并有助于预防药物诱发的疾病。本研究的目的是建立中国新生儿和婴幼儿万古霉素有效给药的PPK模型。使用PPK建模工具Phoenix NLME对2011年至2016年期间重庆医科大学附属儿童医院收治患者回顾性收集的人口统计学和常规临床药代动力学(PK)数据进行评估。2017年1月至6月期间收治入院患者的数据用于验证研究,最终模型还在另一家医院的2例患者中进行了初步验证。初始PPK分析纳入了316例患者的421份血清样本。建立了一个二室PPK模型,并用指数误差模型描述清除率的个体间变异性。残差变异性用加法模型描述。通过内部和外部模型评估证明最终的PPK模型有效。值得注意的是,中国新生儿和婴幼儿万古霉素的清除率和血药浓度可能高于白种人。在此,我们描述了中国新生儿和婴幼儿万古霉素准确PPK模型的建立,该模型可能作为这一特定儿科人群的给药算法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c29/5739632/af263925da91/oncotarget-08-105211-g001.jpg

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