基于生理学的托法西提尼布在人类的药理动力学模拟,使用从单个物种功能衰竭模型的推断
Sung Hun Bae1,2, So Yeon Park3, Hyeon Gyeom Choi1
1College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Republic of Korea.
Pharmaceutics
|July 30, 2025
概括
基于生理学上的药理动力学 (PBPK) 模拟准确地预测了脏衰竭患者的托法西提尼布度. 这种方法有助于优化托法西提尼布剂量以获得有效的治疗.
科学领域:
- 药理动力学 药理动力学
- 药物的新陈代谢和处置
- 翻译药理学 翻译药理学
背景情况:
- 托法西提尼布是一种Janus激酶1和3抑制剂,用于类风湿性关节炎.
- 功能衰竭可能会改变药物的药理动力学,需要调整剂量.
- 预测建模可以为特定患者群体的剂量策略提供信息.
研究的目的:
- 预测tofacitinib的血度和功能性参数在功能衰竭患者.
- 为此目的评估基于生理学的药理动力学 (PBPK) 模拟的实用性.
- 为了比较PBPK模拟与传统方法,如德德里克图形分析.
主要方法:
- 使用PK-Sim和Simcyp的生理学基础的药理动力学 (PBPK) 模拟.
- 从临床前数据中对单个物种进行推断.
- 模拟结果与已发表的临床数据进行比较.
- 传统的德德里克情节分析.
主要成果:
- PBPK模拟与观察到的法西提尼布的血度和关键药理学参数 (AUC,Cmax,Tmax) 非常相匹配.
- 模拟与观察的比率在0.5-2.0倍的误差范围内.
- PBPK模拟显示了比德里克图形分析更高的准确性.
结论:
- 用单个物种抽取进行的PBPK模拟有效地估计了功能衰竭中tofacitinib的药理动力学.
- 这种预测方法支持优化托法西提尼布剂量和剂量方案.
- 考虑患者特定的病理生理特征对于有效的药物治疗至关重要.
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