人口药理动力学分析证实SB16与参考denosumab的生物相似性
Seungchan Choi1,2, Suemin Park1, Jinah Jung3
1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
这项研究对SB16的药理动力学 (PK) 和药理动力学 (PD) 进行了比较. 结果显示SB16与DEN相似,支持其在骨质疏松症治疗中的使用.
科学领域:
- 药理动力学和药理动力学
- 生物相似性评估
- 药物开发
背景情况:
- 对药物开发来说,评估群体的药理动力学 (PK) 和药理动力学 (PD) 是至关重要的.
- 评估生物相似性需要强大的PK/PD建模.
- 德诺苏马布 (DEN) 是骨质疏松症的关键治疗方法.
研究的目的:
- 评估德诺苏马布 (DEN) 的群体PK/PD.
- 使用人口PK/PD方法评估SB16与DEN的生物相似性.
- 分析共变量对PK/PD参数的影响.
主要方法:
- 使用非线性混合效应群体PK/PD序列建模方法.
- 从健康的志愿者和患有骨质疏松症的绝经后妇女收集的数据.
- 采用了具有近似稳定状态 (QSS) 的两部分目标介导药物排放 (TMDD) 模型和间接反应模型.
主要成果:
- 在PK/ PD模型中,充分描述了德诺苏马布 (DEN) 暴露和骨矿物质密度 (BMD) 的变化.
- 观察到对PK的共变效应 (种族,体重),但对BMD变化的影响很小.
- 在SB16和DEN之间没有发现PK/ PD参数或BMD变化.
结论:
- 开发的PK/PD模型准确地描述了denosumab (DEN) 的行为.
- 与DEN相比,SB16表现出类似的PK和BMD变化.
- 这些发现支持SB16作为骨质疏松症治疗中的潜在替代品.
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