Li Mengting, Gao Liuliu, Wang Zuo, Zeng Lingkong, Chen Chen, Wang Jun, Li Sichan, Liu Maochang, Wang Yang
Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Neonatology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Pharmacol. 2024 Nov 27;15:1470350. doi: 10.3389/fphar.2024.1470350. eCollection 2024.
The aim of this study was to develop a population pharmacokinetic model for ceftazidime in critically ill children in the pediatric intensive care unit (PICU) and optimize an appropriate dosing regimen for this population.
We performed a prospective pharmacokinetic study on critically ill children aged 0.03-15 years. A population pharmacokinetic model was developed using the NLME program. Statistical and graphical methods were used to assess the stability and predictive performance of the model. Monte Carlo simulations were conducted to determine the optimal ceftazidime dosing regimen to achieve 70% T > minimum inhibitory concentration (MIC).
This study included 88 critically ill children and 100 ceftazidime serum concentrations. The pharmacokinetic characteristics of ceftazidime were best described by a one-compartment linear elimination model. The weight and estimated glomerular filtration rate (eGFR) were determinant covariates for the clearance (CL) of ceftazidime. The recommended ceftazidime dosage regimens achieved a probability of target attainment (PTA) >90% for critically ill children at MIC values of 2, 4, and 8 mg/L. For bacterial infection at an MIC of 16 mg/L, it is difficult to achieve effective pharmacodynamic (PD) targets with the commonly used dose of ceftazidime.
The population pharmacokinetic model of ceftazidime was established in critically ill children. Based on this model, we recommend evidence-based, individualized dosing regimens for subgroups with different weights and renal functions. The current daily dosage for children adequately meets the treatment requirements for MICs of 2, 4, and 8 mg/L, while for bacterial infection at an MIC of 16 mg/L, an elevated dosage regimen may be required.
https://www.medicalresearch.org.cn/login, Identifier MR-42-22-000220.
本研究旨在建立小儿重症监护病房（PICU）危重症患儿头孢他啶的群体药代动力学模型，并为该群体优化合适的给药方案。
我们对0.03 - 15岁的危重症患儿进行了一项前瞻性药代动力学研究。使用NLME程序建立群体药代动力学模型。采用统计和图形方法评估模型的稳定性和预测性能。进行蒙特卡洛模拟以确定达到70% T＞最低抑菌浓度（MIC）的最佳头孢他啶给药方案。
本研究纳入了88例危重症患儿和100个头孢他啶血清浓度数据。头孢他啶的药代动力学特征用单室线性消除模型描述最佳。体重和估计肾小球滤过率（eGFR）是头孢他啶清除率（CL）的决定性协变量。对于MIC值为2、4和8 mg/L的危重症患儿，推荐的头孢他啶给药方案实现目标达成概率（PTA）＞90%。对于MIC为16 mg/L的细菌感染，常用剂量的头孢他啶难以实现有效的药效学（PD）目标。
在危重症患儿中建立了头孢他啶的群体药代动力学模型。基于该模型，我们推荐针对不同体重和肾功能亚组的循证、个体化给药方案。目前儿童的每日剂量足以满足MIC为2、4和8 mg/L时的治疗需求，而对于MIC为16 mg/L的细菌感染，可能需要提高给药方案。
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