基于药物开发的模型:HSK21542 PBPK模型支持特定人群的剂量决定
Miao Zhang1, Zihan Lei2, Xueting Yao3
1Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China; Department of Pharmaceutical Sciences, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA 02115, United States.
概括
一个新的药理动力学模型预测了HKS21542的暴露. 在/肝功能障碍患者和老年人中,全身暴露增加,但在儿科患者中减少,指导剂量调整.
科学领域:
- 药理动力学和药物新陈代谢
- 临床药理学 临床药理学
- 翻译医学是一种翻译医学.
背景情况:
- HKS21542,卡帕阿片类受体激活剂,正在临床开发中用于抗受和抑制.
- 了解HKS21542在特殊人群中的全身暴露是非常重要的,因为它的指示和消除特征.
研究的目的:
- 为HKS21542.2.开发一个基于生理学的药理动力学 (PBPK) 模型.
- 评估HKS21542在患有功能障碍,肝功能障碍,老年人和儿科患者群体中的全身暴露.
主要方法:
- 开发了HKS21542的PBPK模型,使用了体外代谢和运输数据,以及体内消除机制.
- 在各种特殊人群中模拟HKS21542系统性暴露.
主要成果:
- 在中度至重度功能障碍 (52-71% AUC 增加),轻度至重度肝功能障碍 (46-77% AUC 增加) 和老年人 (45-85% AUC 增加) 中预计会增加 HKS21542 的全身暴露.
- 由于生理差异,预计儿科患者 (0-17岁) 的全身暴露减少了20-37%,由于生理差异.
- 观察到的老年人暴露与模型预测密切匹配.
结论:
- PBPK模型准确地预测了特殊人群中的HKS21542暴露.
- 剂量方案成功设计用于和肝功能障碍,支持临床试验.
- 需要仔细考虑减少儿科暴露,以防止治疗失败.
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