From the Institute for Clinical Pharmacodynamics, Inc. Schenectady, NY.
West Virginia University School of Medicine, Department of Pediatrics, Morgantown, WV.
Pediatr Infect Dis J. 2021 Nov 1;40(11):997-1003. doi: 10.1097/INF.0000000000003296.
Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced-generation, broad-spectrum, intravenous cephalosporin, which is currently approved for the treatment of adults with hospital-acquired or community-acquired pneumonia.
Noncompartmental pharmacokinetics and safety were analyzed from 2 recently completed pediatric studies, a single-dose, phase 1 study in neonates and infants up to 3 months of age (7.5 mg/kg) and a phase 3 study in patients 3 months to 17 years of age with pneumonia (10-20 mg/kg with a maximum of 500 mg per dose every 8 hours for up to 14 days).
Total ceftobiprole plasma concentrations peaked at the end of infusion. Half life (median ranging from 1.9 to 2.9 hours) and overall exposure (median AUC ranging from 66.6 to 173 μg•h/mL) were similar to those in adults (mean ± SD, 3.3 ± 0.3 hours and 102 ± 11.9 μg•h/mL, respectively). Calculated free-ceftobiprole concentrations in the single-dose study remained above a minimum inhibitory concentration (MIC) of 4 mg/L (fT > MIC of 4 mg/L) for a mean of 5.29 hours after dosing. In the pneumonia study, mean fT > MIC of 4 mg/L was ≥5.28 hours in all dose groups. Ceftobiprole was well tolerated in both studies.
Pharmacokinetic parameters of ceftobiprole characterized in the pediatric population were within the range of those observed in adults. In the pneumonia study, the lowest percentage of the dosing interval with fT > MIC of 4 mg/L was 50.8%, which suggests that pharmacokinetic-pharmacodynamic target attainment can be sufficient in pediatric patients. Ceftobiprole was well tolerated.
头孢托罗匹酯是前体药物头孢托罗匹酯美多卡利的活性成分，是一种新型广谱静脉用头孢菌素，目前已批准用于治疗成人医院获得性或社区获得性肺炎。
对最近完成的两项儿科研究中的非房室药代动力学和安全性数据进行分析，这两项研究分别为一项新生儿和 3 个月以下婴儿的单剂量、Ⅰ期研究（7.5mg/kg）和一项 3 个月至 17 岁肺炎患者的Ⅲ期研究（10-20mg/kg，最大剂量为 500mg/次，每 8 小时 1 次，最长 14 天）。
总头孢托罗匹酯血浆浓度在输注结束时达到峰值。半衰期（中位数范围为 1.9-2.9 小时）和总体暴露量（中位数 AUC 范围为 66.6-173μg•h/mL）与成人相似（均值±标准差分别为 3.3±0.3 小时和 102±11.9μg•h/mL）。在单剂量研究中，计算得出的单次给药后头孢托罗匹酯游离浓度在 5.29 小时内均保持在最低抑菌浓度（MIC）4mg/L 以上（fT＞MIC 4mg/L）。在肺炎研究中，所有剂量组的平均 fT＞MIC 4mg/L均≥5.28 小时。在这两项研究中，头孢托罗匹酯均具有良好的耐受性。
在儿科人群中描述的头孢托罗匹酯药代动力学参数在成人观察到的范围内。在肺炎研究中，fT＞MIC 4mg/L 的给药间隔百分比最低为 50.8%，这表明在儿科患者中，药代动力学-药效学目标的实现可能是足够的。头孢托罗匹酯具有良好的耐受性。
