在新生儿人口中基于生理学上的药理动力学建模 - - 当前的进展,挑战和机遇
Jean Dinh1, Trevor N Johnson1, Manuela Grimstein2
1Certara UK Limited, Sheffield S1 2BJ, UK.
Pharmaceutics
|November 25, 2023
概括
基于生理学的药理动力学 (PBPK) 建模有助于在新生儿中优化药物剂量. 本次审查确定了对这一脆弱人群的PBPK数据需求,解决了新生儿药物开发方面的知识差距.
科学领域:
- 药理动力学和药物新陈代谢
- 儿科药理学 儿科药理学
- 计算生物学 计算生物学
背景情况:
- 基于生理学的药理动力学 (PBPK) 建模预测了体内的药物行为.
- 由于临床试验数据有限,PBPK对儿科患者,特别是新生儿至关重要.
- 现有的知识差距阻碍了新生儿准确的PBPK模型预测.
研究的目的:
- 审查新生儿PBPK模型中的变异性来源.
- 为了总结PBPK的新生儿本体发生学数据.
- 为了确定未来新生儿研究的关键数据缺口.
主要方法:
- 对PBPK建模原理的文献综述.
- 对新生儿现有的生理和药物特性数据的分析.
- 确定影响药物处置的与本体发生有关的因素.
主要成果:
- 变化的来源包括器官的成熟和药物代谢酶.
- 对于新生儿的酶活性和输送体表达的数据有限.
- 显著的数据差距阻碍了对新生儿药物剂量的准确PBPK预测.
结论:
- 新生儿PBPK模型需要全面的本体生成数据以获得准确性.
- 进一步的研究是必要的,以填补新生儿生理学和药物处置的数据缺口.
- 改进的PBPK模型将增强安全有效的新生儿药物治疗.
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