建立一个适应剂量模拟框架,以帮助选择剂量和时间表
Richard Hooijmaijers1, Ridhi Parasrampuria2, Eleonora Marostica1
1Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, The Netherlands.
本教程介绍了一个适应剂量模拟框架,以优化药物治疗方案. 它有助于平衡治疗益处和不良影响,通过评估各种剂量策略在.
科学领域:
- 制药指标 (Pharmacometrics) 是一个指标.
- 计算药理学计算药理学
- 药物开发 药物开发
背景情况:
- 优化新疗法的剂量方案,特别是在治疗窗口狭窄的瘤学中,对于最大限度地提高临床益处和最大限度地减少不良影响至关重要.
- 建模和模拟提供了有价值的in silico工具来评估各种剂量场景,旨在减少毒性和治疗中止.
研究的目的:
- 介绍适应剂量模拟框架的逐步开发,以优化药物剂量和时间表.
- 提供实施该框架的实际例子,使用mrgsolve进行药物开发决策.
主要方法:
- 开发了一个自适应模拟框架,整合了药理动力学,药理动力学 (生物标志物,疗效,安全性) 和可变性模型.
- 包括对个体间和个体内变异性和共变量影响的评估,允许用户定义的模型扩展 (例如,组合疗法).
- 利用随后的自适应模拟来研究起始剂量,间隔和事件驱动的修改对各种终点的影响.
主要成果:
- 通过实践示例证明了框架在探索剂量和时间表优化方面的实用性.
- 展示了自适应模拟如何评估不同剂量策略和修改的影响.
- 产生了洞察力,以量化建议优化方案,平衡有效性和安全性.
结论:
- 适应模拟框架有助于定量提出剂量和治疗方案,以优化新疗法的益处风险概况.
- 促进在剂量选择,疗程设计和剂量修改建议方面做出明智的决策.
- 通过提供模拟衍生的对剂量优化的洞察力,支持进一步评估治疗策略.
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