剂量优化由PBPK建模提供信息:最先进的技术和未来
Karen Rowland Yeo1, Eva Gil Berglund2, Yuan Chen3
1Certara UK Limited (Simcyp Division), Sheffield, UK.
Clinical pharmacology and therapeutics
|April 30, 2024
概括
基于模型的药物开发 (MIDD) 使用定量方法指导药物试验. 基于生理学的药理动力学 (PBPK) 建模对于优化不同人群中药物剂量越来越重要.
科学领域:
- 药理动力学和药物开发
- 量化药理学 量化药理学
- 监管科学 监管科学
背景情况:
- 基于模型的药物开发 (MIDD) 是药物开发和监管审查的关键定量方法.
- 基于生理学的药理动力学 (PBPK) 建模是MIDD的一个关键工具,传统上专注于药物相互作用 (DDI) 和剂量调整.
- 越来越多的人对PBPK的信任正在将其应用范围扩大到DDI之外.
研究的目的:
- 审查目前对药物开发中PBPK应用的监管接受情况.
- 讨论PBPK模型在各种人群中对剂量建议的扩展效用.
- 探索PBPK在监管决策中的未来挑战和机遇,包括弱势群体和临床试验多样性.
主要方法:
- 对PBPK应用程序的当前文献和案例研究的审查.
- 分析与PBPK相关的监管提交和指导文件.
- 关于PBPK在药物开发中的进展和未来方向的观点.
主要成果:
- 监管机构越来越多地接受PBPK建模,用于告知临床试验设计,包括剂量选择和优化.
- 正在成功地应用PBPK模型,为不同患者群体 (年龄,遗传学,疾病状态) 提供剂量建议.
- 案例研究证明了PBPK在监管提交中的实用性.
结论:
- PBPK建模是优化药物剂量的强大工具,并为监管决策提供信息.
- 将PBPK应用扩展到研究不足的人群中,并增强临床试验多样性是未来的关键目标.
- 持续的科学进步和监管合作将推动PBPK的更广泛的采用.
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