在儿童群体中对单克隆抗体药理动学的研究和使用平台PBPK模型进行表征
Mokshada Kumar1, Sravani Lanke1, Dhaval K Shah2
1Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences,, The State University of New York at Buffalo, 455 Pharmacy Building, Buffalo, New York, 14214-8033, USA.
The AAPS journal
|January 6, 2026
概括
儿科患者的单克隆抗体 (mAbs) 初始度较低. 开发了一个基于生理学的平台性药理动力学 (PBPK) 模型,以优化儿童的mAb剂量.
科学领域:
- 药理动力学 药理动力学
- 儿科药理学 儿科药理学
- 计算生物学 计算生物学
背景情况:
- 单克隆抗体 (mAbs) 在儿童群体中越来越多地使用.
- 了解特定年龄的药理动力学 (PK) 差异对于安全有效的剂量至关重要.
- 关于儿科mAb PK的现有数据通常是有限的.
研究的目的:
- 调查年龄对mAbs.儿童PK的影响.
- 开发一个平台生理学基础的药理动力学 (PBPK) 模型用于儿科mAb剂量.
- 为了支持儿童患者mAbs的最佳剂量策略.
主要方法:
- 文献审查以确定儿科mAb PK数据.
- 开发一个平台PBPK模型.
- 模型验证使用儿科患者现有的PK数据.
- 将PBPK模型集成到R Shiny应用程序中.
主要成果:
- 儿科患者的初始mAb度在体重正常化剂量下比成人低20-40%.
- 婴儿和新生儿的线性PK mAbs的体重正常化清除高达45%以上.
- 在儿科患者中,非线性PK mAbs显示体重正常化清除显著更快 (高达350%以上).
- 在小儿患者 (0.13-17岁) 中,PBPK模型充分表征了11mAbs的血PK,%PE<35.
- 该模型证明了抗体PK的先验预测 (%PE <35) 是合理的.
结论:
- 年龄显著影响儿科患者的mAb PK,清除有显著差异,特别是在较年轻的婴儿中.
- 开发的平台PBPK模型有效地描述了儿科mAb PK,并支持个性化剂量.
- 即使数据有限,R Shiny应用程序提供了一个可访问的工具来模拟mAb PK并优化儿科剂量,即使数据有限.
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