在Padsevonil临床开发中实施以患者为中心的采样技术的临床桥梁研究和建模方法
Hester Kramer1, Ceyhun Bicer2, Christian Otoul1
1Early Solutions, Development Sciences, UCB Biopharma SRL, Chemin du Foriest, B-1420, Braine l'Alleud, Belgium.
The AAPS journal
|November 16, 2023
概括
使用Mitra®设备进行体积吸收微采样 (VAMS) 有效地弥合了药理动力学研究的血液和血度. 这种经过验证的方法支持在临床试验中使用VAMS作为唯一的血液采样技术.
科学领域:
- 药理动力学和药物开发
- 临床药理学 临床药理学
- 生物医学工程 生物医学工程
背景情况:
- 在临床试验中,体积吸收微采样 (VAMS) 与传统血液采样相比,为药理动力学 (PK) 分析提供了优势.
- 使用VAMS技术的Mitra®设备在开发抗发作药物候选物Padsevonil (PSL) 期间使用.
研究的目的:
- 建立一种方法,将PSL的血度 (来自静脉血液) 与血度 (来自VAMS) 相对应.
- 为了验证Mitra®设备作为临床环境中唯一的血液PK采样方法.
主要方法:
- 从健康的志愿者和患者中收集了配对血液 (Mitra®) 和血样本.
- 分析涉及血液与血的比率 (B/P),线性回归,布兰德-阿尔特曼分析和线性混合效应模型.
- 在体外和体外B/P比率进行了比较,并开发并验证了一种预测模型.
主要成果:
- 在体内观察到的B/P比率和偏差与体内测量结果一致.
- 确定了对B/P的显著时间影响,采样时间是混合效应模型中的关键共变量.
- 经过验证的模型从血度准确预测了血度,平均偏差为<9%.
结论:
- 开发的桥梁方法成功地将VAMS血度与PSL的传统血度相关联.
- 这种经过验证的方法支持的Mitra® VAMS设备可以在临床试验中可靠地被用作唯一的血液PK采样技术.
- 这有助于在药物开发中更高效,更为患者友好的样本采集.
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