Pediatric Research Institute, Children's Hospital of Hebei Province, Shijiazhuang, China.
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Antimicrob Agents Chemother. 2018 Mar 27;62(4). doi: 10.1128/AAC.02486-17. Print 2018 Apr.
Ceftazidime, a third-generation cephalosporin, can be used for the treatment of adults and children with infections due to susceptible bacteria. To date, the pediatric pharmacokinetic data are limited in infants, and therefore we aimed to evaluate the population pharmacokinetics of ceftazidime in infants and to define the appropriate dose to optimize ceftazidime treatment. Blood samples were collected from children treated with ceftazidime, and concentrations of the drug were quantified by high-performance liquid chromatography with UV detection (HPLC-UV). A population pharmacokinetic analysis was performed using NONMEM software version 7.2.0). Fifty-one infants age range, 0.1 to 2.0 years were included. Sparse pharmacokinetic samples = 90 were available for analysis. A one-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that body weight and creatinine clearance (CL) were significant covariates influencing ceftazidime clearance. Monte Carlo simulation demonstrated that the currently used dosing regimen of 50 mgkg twice daily was associated with a high risk of underdosing in infants. In order to reach the target of 70% of the time that the free antimicrobial drug concentration exceeds the MIC (), 25 mg/kg every 8 h (q8h) and 50 mg/kg q8h were required for MICs of 4 and 8 mg/liter, respectively. The population pharmacokinetic characteristics of ceftazidime were evaluated in infants. An evidence-based dosing regimen was established based on simulation.
头孢他啶，一种第三代头孢菌素，可用于治疗成人和儿童因敏感菌引起的感染。迄今为止，儿科药代动力学数据在婴儿中有限，因此我们旨在评估婴儿头孢他啶的群体药代动力学，并确定适当的剂量以优化头孢他啶治疗。采集接受头孢他啶治疗的儿童的血样，并通过高效液相色谱法与紫外检测（HPLC-UV）定量药物浓度。使用 NONMEM 软件版本 7.2.0 进行群体药代动力学分析。共纳入 51 名年龄在 0.1 至 2.0 岁的婴儿。可用于分析的稀疏药代动力学样本量为 90 个。具有一级消除的单室模型显示与数据拟合最佳。协变量分析表明，体重和肌酐清除率（CL）是影响头孢他啶清除率的重要协变量。蒙特卡罗模拟表明，目前使用的 50mg/kg 每天两次的给药方案在婴儿中存在剂量不足的高风险。为了达到游离抗菌药物浓度超过 MIC 的时间的目标（），对于 MIC 分别为 4 和 8 mg/L，需要每 8 小时 25mg/kg（q8h）和 50mg/kg q8h。评估了婴儿头孢他啶的群体药代动力学特征。基于模拟建立了基于证据的给药方案。
