Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA.
Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium.
Antimicrob Agents Chemother. 2021 Oct 18;65(11):e0120621. doi: 10.1128/AAC.01206-21. Epub 2021 Aug 16.
Ceftobiprole is an advanced-generation cephalosporin for intravenous administration with activity against Gram-positive and Gram-negative organisms. A population pharmacokinetic (PK) model characterizing the disposition of ceftobiprole in plasma using data from patients in three pediatric studies was developed. Model-based simulations were subsequently performed to assist in dose optimization for the treatment of pediatric patients with hospital-acquired or community-acquired pneumonia. The population PK data set comprised 518 ceftobiprole plasma concentrations from 107 patients from 0 (birth) to 17 years of age. Ceftobiprole PK was well described by a three-compartment model with linear elimination. Ceftobiprole clearance was modeled as a function of glomerular filtration rate; other PK parameters were scaled to body weight. The final population PK model provided a robust and reliable description of the PK of ceftobiprole in the pediatric study population. Model-based simulations using the final model suggested that a ceftobiprole dose of 15 mg/kg of body weight infused over 2 h and administered every 12 h in neonates and infants <3 months of age or every 8 h in older pediatric patients would result in a ceftobiprole exposure consistent with that in adults and good pharmacokinetic-pharmacodynamic target attainment. The dose should be reduced to 10 mg/kg every 12 h in neonates and infants <3 months of age who weigh <4 kg to avoid high exposures. Extended intervals and reduced doses may be required for pediatric patients older than 3 months of age with renal impairment.
头孢托罗是一种用于静脉注射的新型头孢菌素，对革兰氏阳性菌和革兰氏阴性菌均具有活性。本研究建立了一个群体药代动力学（PK）模型，用于描述三种儿科研究中患者的头孢托罗在血浆中的分布情况。随后进行了基于模型的模拟，以协助优化治疗儿童医院获得性或社区获得性肺炎的剂量。该群体 PK 数据集包含了 107 名 0（出生）至 17 岁患者的 518 个头孢托罗血浆浓度。头孢托罗 PK 很好地由一个具有线性消除的三房室模型描述。头孢托罗清除率被建模为肾小球滤过率的函数；其他 PK 参数按体重缩放。最终的群体 PK 模型为儿科研究人群中头孢托罗的 PK 提供了一个稳健而可靠的描述。使用最终模型进行的基于模型的模拟表明，新生儿和<3 个月大的婴儿每 12 小时给予 15mg/kg 体重的头孢托罗，或年龄较大的儿科患者每 8 小时给予一次，剂量为 15mg/kg 体重，输注 2 小时，可使头孢托罗暴露量与成人一致，并达到良好的药代动力学-药效学目标。对于体重<4kg 的<3 个月大的新生儿，应将剂量减少至每 12 小时 10mg/kg，以避免高暴露。对于 3 个月以上有肾功能损害的儿科患者，可能需要延长间隔和减少剂量。
