Shen Kai, Fan Yaxin, Yang Minjie, Chen Yuancheng, Tao Jinhao, Lu Guoping, Zhang Hong, Huang Qiwei, Zhang Jing
Institute of Antibiotics, Huashan Hospital, Fudan University, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission of People's Republic of China, Shanghai, China.
Department of Critical Care Medicine, Children's Hospital of Fudan University, Shanghai, China.
Front Pharmacol. 2021 Apr 15;12:648668. doi: 10.3389/fphar.2021.648668. eCollection 2021.
The aim of this study was to establish the population pharmacokinetics (PK) model of Vancomycin for Chinese pediatric patients which can extrapolate to whole age periods by bridging the published adult population PK model and the established pediatric population PK model. The final consolidated population PK model was used to explore the correlation of pharmacokinetics/pharmacodynamics (PK/PD) indices and efficacy of vancomycin and to provide evidence for the optimized regimen of vancomycin in Chinese pediatric patients with Gram-positive bacterial infection. 108 pediatric patients with Gram-positive infections from 2 pediatric hospitals in China in the first period of the prospective multi-center vancomycin clinical observational study were enrolled to establish the population PK model. A one-compartment population PK model was established and validated. The correlation between vancomycin PK/PD indices [trough concentration (C), peak concentration (C), 0-24 h area under the curve (AUC) and the area under the curve to minimum inhibitory concentration ratio (AUC/MIC)] and the overall clinical outcomes (clinical efficacy and microbiological efficacy) in Chinese pediatric patients were evaluated. There is no significant correlation between PK/PD indices and clinical efficacy or microbiological efficacy. Considering the high clinical effective rate (>90%) and median AUC/MIC values of 200-300, Chinese pediatric patients with Gram-positive bacterial infection may be suitable for lower AUC/MIC target value compared to the target value of 400-600 recommended by IDSA guideline. Different optimal dose regimen of vancomycin for Chinese pediatric patients should be considered. Further evaluation in more prospective studies will be needed.
本研究的目的是建立中国儿科患者万古霉素的群体药代动力学（PK）模型，通过衔接已发表的成人群体PK模型和已建立的儿科群体PK模型，该模型可外推至整个年龄段。最终整合的群体PK模型用于探索万古霉素的药代动力学/药效学（PK/PD）指标与疗效之间的相关性，并为中国革兰氏阳性菌感染儿科患者万古霉素的优化给药方案提供依据。在前瞻性多中心万古霉素临床观察研究的第一阶段，纳入了中国两家儿科医院的108例革兰氏阳性感染儿科患者，以建立群体PK模型。建立并验证了单室群体PK模型。评估了中国儿科患者万古霉素PK/PD指标[谷浓度（C）、峰浓度（C）、0至24小时曲线下面积（AUC）以及曲线下面积与最低抑菌浓度之比（AUC/MIC）]与总体临床结局（临床疗效和微生物学疗效）之间的相关性。PK/PD指标与临床疗效或微生物学疗效之间无显著相关性。考虑到临床有效率较高（>90%）且AUC/MIC中位数为200 - 300，与美国感染病学会（IDSA）指南推荐的400 - 600目标值相比，中国革兰氏阳性菌感染儿科患者可能适合较低的AUC/MIC目标值。应考虑针对中国儿科患者的不同万古霉素最佳给药方案。需要在更多前瞻性研究中进行进一步评估。
