社区获得性肺炎儿童头孢曲松的群体药代动力学和剂量优化。
Population pharmacokinetics and dose optimization of ceftriaxone for children with community-acquired pneumonia.
机构信息
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, No. 44, Wenhua West Road, Jinan, Shandong Province, China.
Department of Respiratory Care, Children's Hospital of Hebei Province affiliated to Hebei Medical University, Shijiazhuang, China.
出版信息
Eur J Clin Pharmacol. 2020 Nov;76(11):1547-1556. doi: 10.1007/s00228-020-02939-4. Epub 2020 Jun 25.
PURPOSE
To assess ceftriaxone population pharmacokinetics in a large pediatric population and describe the proper dose for establishing an optimized antibiotic regimen.
METHODS
From pediatric patients using ceftriaxone, blood samples were obtained and the concentration was measured using high-performance liquid chromatography ultraviolet detection. The NONMEM software program was used for population pharmacokinetic analysis, for which data from 99 pediatric patients (2 to 12 years old) was collected and 175 blood concentrations were obtained.
RESULTS
The best fit with the data was shown by the one-compartment model with first-order elimination. According to covariate analysis, weight had a significant impact on the clearance of ceftriaxone. Using Monte Carlo simulation, in a pediatric population with community-acquired pneumonia, a dose regimen of 100 mg/kg every 24 h produced satisfactory target attainment rates while remaining within the required minimum inhibitory concentration (2 mg/L).
CONCLUSION
Population pharmacokinetics of ceftriaxone was evaluated in children and an optimum dosing regimen was constructed on the basis of the pharmacokinetics-pharmacodynamics model-based approach.
目的
评估头孢曲松在大型儿科人群中的群体药代动力学,并描述建立优化抗生素治疗方案的合适剂量。
方法
从使用头孢曲松的儿科患者中采集血样,并使用高效液相色谱紫外检测法测定浓度。采用 NONMEM 软件程序进行群体药代动力学分析,共收集了 99 例 2 至 12 岁儿科患者的数据,并获得了 175 个血药浓度。
结果
数据最佳拟合模型为单室模型加一级消除。根据协变量分析,体重对头孢曲松清除率有显著影响。通过蒙特卡罗模拟,在患有社区获得性肺炎的儿科人群中,每 24 小时给予 100mg/kg 的剂量方案可达到满意的靶标浓度,同时仍在所需最低抑菌浓度(2mg/L)范围内。
结论
基于药代动力学-药效学模型方法,评估了儿童头孢曲松的群体药代动力学,并构建了最佳的给药方案。