基于生理学的维生素B-12的药物动力学建模,包括机械吸收:怀孕期间摄入量估计的示例应用
Mian Zhang1, Lisa M Almond1, Hannah M Jones1
1Certara Predictive Technologies Division, Certara UK Limited, Sheffield, United Kingdom.
这项研究开发了一种药理动力学模型,以了解维生素B-12的吸收. 该模型表明,孕妇可能需要每天150微克,分为几剂量,以保持足够的维生素B-12水平.
科学领域:
- 药理动力学和营养科学 药理动力学和营养科学
- 生理学基础的药理动力学 (PBPK) 建模
背景情况:
- 维生素B-12 (科巴胺) 对神经功能,造血和DNA合成至关重要.
- 口服吸收涉及内在因子 (IF) 依存和被动扩散途径.
- 低于最佳的维生素B-12状态是令人担忧的,特别是在孕妇中.
研究的目的:
- 为维生素B-12吸收开发PBPK模型.
- 为了评估维生素B-12摄入需求在改变的生理状态,如怀孕.
主要方法:
- 构建了一个PBPK模型,整合了维生素B-12-IF结合,素介导吸收和被动扩散.
- 该模型模拟了不同剂量的维生素B-12吸收.
- 模拟预测了在IF分泌减少和全身清除增加的条件下血维生素B-12度.
主要成果:
- 该模型准确地反映了非线性维生素B-12吸收及其对IF和库比林的依赖.
- 口服剂量为1,2,1000微克的模拟吸收百分比分别为83%,63%和1%.
- 怀孕模拟表明需要每天150μg,分为三次50μg剂量,以达到足够的血维生素B-12度 (>300 pmol/L).
结论:
- PBPK建模提供了对维生素B-12吸收的机制性理解.
- 这种方法可以为改变生理需求的人群提供维生素B-12摄入量建议.
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