基于单个样本和人群药动力学模型的托波特干清除:适用于儿科高风险神经母细胞瘤临床试验
Olivia Campagne1, Huiyun Wu2, Jianrong Wu2
1Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Pediatric blood & cancer
|September 4, 2023
概括
一种使用单个血液样本的新方法可以准确估计个体的托波特坎清除值,有助于儿童癌症治疗. 这种方法有助于更多的患者达到所需的托波特坎全身暴露 (SE),以获得更好的结果.
科学领域:
- 药理动力学和药理动力学
- 儿科瘤学 儿科瘤学
- 药物开发 药物开发
背景情况:
- 托波特干是一种抗瘤药物,在儿科瘤中表现出全身暴露 (SE) 依赖的活性.
- 托波特坎患者间显著的药理动力学变异使得实现所需的SE变化变得复杂.
- 准确的剂量对于最大限度地提高疗效和最大限度地降低毒性至关重要.
研究的目的:
- 更新托波特干种群的药理动力学模型.
- 评估从单个血液样本中确定个人托波特干清除的可行性.
- 将这种方法应用于神经母细胞瘤试验数据,用于暴露-反应分析.
主要方法:
- 使用13项儿科研究的数据更新了以前的人口药理动力学和协变模型.
- 采用基于模拟的贝叶斯分析来评估单个样本清除值的估计.
- 分析了ANBL0532神经母细胞瘤试验中的药理动力学样本,以估计个人托波特坎SE.
主要成果:
- 更新后的模型纳入了身体表面积 (BSA),年龄和功能对托波特坎清除的影响.
- 单样贝叶斯分析以很好的精度 (MAPE ≤16.2%) 和低偏差 (MPE ≤7.2%) 估计了个体的托波特干净度.
- 随着同时使用环胺和托波特干,观察到高达45h·ng/mL的托波特干SE的早期反应增加.
结论:
- 简化单样方法可以指导治疗期间的托波特干剂量.
- 这种方法有助于更多的患者实现目标SE.
- 改进的剂量策略可以提高儿科瘤学的治疗结果.
相关概念视频
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00:56One-Compartment Open Model for IV Bolus Administration: Estimation of Clearance
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00:59Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
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01:25Clearance Models: Compartment Models
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01:26Pharmacokinetic Models: Comparison and Selection Criterion
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