单一时间点剂量计的准确性和精度分析,使用生理学基础的药物动力学建模和非线性混合效应建模
Indra Budiansah1, Deni Hardiansyah2,3, Ade Riana1,4
1Faculty of Mathematics and Natural Sciences, Medical Physics and Biophysics Division, Physics Department, Universitas Indonesia, Depok, Indonesia.
使用生理学基础的药理动力学 (PBPK) 模型的单次时间点 (STP) 剂量计表明吸收剂量估计的准确性可接受. 然而,与全时点 (ATP) 配件相比,STP剂量计显示精度降低,这对于优化简化剂量计协议至关重要.
科学领域:
- 核医学是一种核医学.
- 放射性药物剂量测量 放射性药物剂量测量
- 药理动力学 药理动力学
背景情况:
- 准确的吸收剂量 (AD) 估计对于个性化的放射性药物治疗至关重要.
- 基于生理学的药理动力学 (PBPK) 模型与非线性混合效应建模 (NLMEM) 结合,为剂量计提供了一个强大的框架.
- 通过单一时间点 (STP) 方法简化剂量计方案是理想的临床效率.
研究的目的:
- 使用PBPK-NLMEM方法评估STP剂量计的准确性和精度.
- 为了确定[111In]In-DOTA-TATE的STP剂量测量的最佳时间点.
- 为了比较STP剂量计的精度与全时点 (ATP) 剂量计.
主要方法:
- 从接受[111In]In-DOTA-TATE的8名患者获得的生物动力学数据,使用平面光学图和血清活性测量进行了分析.
- 使用NONMEM将PBPK模型与生物动力学数据相匹配,适合性标准包括相对标准误差 (<50%) 和相关性矩阵元素 (<0.8).
- 使用Jackknife方法计算STP吸收剂量 (sADs),并将其与ATP配件的参考ADs (rADs) 进行比较,以评估准确性. 根-平方平均误差 (RMSE) 被最小化以找到最佳时间点.
主要成果:
- 该PBPK-NLMEM方法提供了足够适合生物动力学数据.
- 在注射后48小时的STP剂量测量结果显示,脏 (7±2%) 和瘤 (14±4%) 吸收剂量估计的RMSE最低.
- 与ATP剂量计相比,STP剂量计的精度较低,脏ADS的中位数相对标准误差为6% (STP) 与3% (ATP),瘤ADS为9% (STP) 与4% (ATP).
结论:
- 使用PBPK-NLMEM的单个时间点剂量计为吸收剂量估计提供了可接受的准确性.
- 与ATP剂量计相比,在STP剂量计时观察到精度下降.
- 了解STP剂量计的精度对于开发高效和简化的临床剂量计协议至关重要.
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