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颗粒细胞殖民地刺激因子的人口药理动力学-药理动力学建模,以优化CD34⁺细胞采集的剂量和时间

Xu Jiang¹, Jun Seok Cha^1,2, Byung Hak Jin³

¹Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.

Clinical and translational science

|January 3, 2025

概括

为了优化外围血液干细胞采集,开发了一种对粒细胞殖民地刺激因子 (G-CSF) 的人口药理动力学模型. 模拟表明,每天两次服用5微克/千克的G-CSF疗法可能会改善用于移植的CD34+细胞产量.

科学领域:

药理学药理学是指药理学的学科.
血液学血液学血液学
生物技术是生物技术.

背景情况:

颗粒细胞殖民地刺激因子 (G-CSF) 对于调动外围血液前代细胞进行移植至关重要.
优化G-CSF剂量对于在外周血液干细胞移植 (PBSCT) 中有效采集CD34+细胞至关重要.

研究的目的:

在健康受试者中开发一种群体药理动力学-药理动力学 (PK-PD) 模型用于filgrastim (G-CSF).
优化CD34+细胞采集策略,用于全原PBSCT.

主要方法:

使用53名韩国健康受试者的血filgrastim度和CD34+细胞计数,构建了一个人群PK-PD模型.
菲尔格拉斯蒂姆的药理动力学模型是使用一个带有过渡吸收区的单间线性配置模型来建模的.
使用修改后的弗里伯格模型建模了CD34+细胞动员.

主要成果:

经日志转换的体重被确定为菲尔格拉斯蒂姆的分布量和清除量的显著共变量.
该模型表明,每天两次服用5mcg/kg的G-CSF剂量方案可以比每天一次服用10mcg/kg更高的CD34+细胞计数.
模拟表明最佳剂量达到目标CD34+细胞计数20/μL和50/μL.

结论:

成功开发了G-CSF的强大的PK-PD模型,使CD34+细胞产量能够优化用于PBSCT.
该模型为指导高效的G-CSF剂量方案和CD34+细胞采集策略提供了一个框架.

关键词:

CD34+ CD34+ CD34+ CD34+ CD34+ CD34+ CD34+菲尔格拉斯蒂姆的使用方法颗粒细胞殖民地刺激因子.人口的药理动力学-药理动力学建模.

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