Bayer Healthcare, Berlin, Germany.
Paediatr Drugs. 2012 Jun 1;14(3):189-200. doi: 10.2165/11595430-000000000-00000.
According to the International Conference on Harmonisation guideline E11, pharmacokinetic (PK) bridging studies can be applied to support pediatric drug development. However, for PK studies in infants and children the sampling schedule needs to be optimized to minimize the number of blood samples per individual.
The aim of this study was to describe how clinical trial simulations (CTS) based on adult data were used to select an appropriate sparse-sampling schedule for a future pediatric population PK (popPK) study.
A popPK model for gadobutrol (Gadovist®) was developed using data from a phase I study in adults. This model was used for CTS to select the most appropriate sparse-sampling schedule that met predefined acceptance criteria. This sampling schedule was applied in a pediatric clinical phase I/III study. Non-linear mixed-effects modeling was used for PK modeling and simulations.
An appropriate sampling schedule requiring only three blood samples per patient was selected and successfully applied in a pediatric study with a gadobutrol standard dose of 0.1 mmol/kg bodyweight. A popPK analysis was performed to determine individual PK parameters in the pediatric study population.
A priori evaluation of selected sampling schedules by simulation from adult data provides a useful tool for efficient planning of pediatric studies.
根据国际协调会议指导原则 E11，药代动力学（PK）桥接研究可用于支持儿科药物开发。然而，对于婴儿和儿童的 PK 研究，需要优化采样方案，以尽量减少每个个体的采血次数。
本研究旨在描述如何基于成人数据的临床试验模拟（CTS）来选择未来儿科人群药代动力学（popPK）研究的合适稀疏采样方案。
使用成人 I 期研究的数据开发了用于钆布醇（Gadovist®）的 popPK 模型。该模型用于 CTS 以选择最符合预设接受标准的最合适稀疏采样方案。该采样方案应用于儿科 I/III 期临床研究。采用非线性混合效应模型进行 PK 建模和模拟。
选择了一种仅需每位患者采集 3 个血样的合适采样方案，并成功应用于儿童研究，其中钆布醇标准剂量为 0.1mmol/kg 体重。对儿科研究人群进行了 popPK 分析，以确定个体 PK 参数。
通过从成人数据模拟预先评估选定的采样方案，为高效规划儿科研究提供了有用的工具。
