在怀孕期间优化孕产妇和胎儿抗体暴露和剂量方案,使用生理学基础的药理动力学模型
Miramar Sami Kardouh1, Tyler C Dunlap1, Rui Zhong1
1Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Clinical pharmacology and therapeutics
|April 4, 2025
概括
这项研究开发了一种基于生理学的药理动力学 (PBPK) 模型,以预测孕妇和胎儿的治疗抗体暴露. 该模型有助于优化剂量以维持母亲的治疗,同时最大限度地减少胎儿的暴露.
科学领域:
- 药理动力学和药物新陈代谢
- 生殖毒理学 生殖毒理学
- 免疫学 免疫学 免疫学
背景情况:
- 治疗性抗体在怀孕期间用于各种疾病的非标签.
- 这些抗体对胎儿的暴露和发育风险在很大程度上是未知的.
- 伦理上的约束限制了孕妇群体的随机试验.
研究的目的:
- 开发一种基于生理学的药理动力学 (PBPK) 模型,用于预测怀孕期间母亲和胎儿的抗体暴露.
- 为了将胎盘新生儿Fc受体 (FcRn) 表达纳入模拟IgG转移的模型.
- 评估怀孕期间生物制剂的剂量方案.
主要方法:
- 开发了一种PBPK模型,用于FcRn介导的晶体体抗体转移,具有三个内体体隔间.
- 集成的FcRn表达式数据.
- 校准和验证模型使用成年人,孕妇和婴儿的药理动力学数据.
主要成果:
- 该PBPK模型准确预测了几种治疗抗体 (infliximab,adalimumab,ustekinumab,vidolizumab,etanercept) 的母亲和胎儿度.
- 预测通常在观察到的度的两倍范围内.
- 该框架确定了剂量策略,以平衡母亲的疗效和胎儿的安全.
结论:
- 建立了一个可概括的PBPK框架,以预测生物体的移植性转移.
- 该模型有助于理解胎儿对治疗抗体的暴露.
- 该工具支持在整个怀孕期间为生物药物提供最佳剂量方案.
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