在慢性病中建模甲福明和达帕格利弗洛辛的药理动力学
Andrew Shahidehpour1, Mudassir Rashid1, Mohammad Reza Askari1
1Department of Chemical and Biological Engineering, Illinois Institute of Technology, Chicago, Illinois, USA.
The AAPS journal
|August 19, 2024
概括
这项研究提出了一种新的方法,用于模拟慢性病 (CKD) 和糖尿病患者的药物清除. 该方法使用现有的数据和机制模型来估计药物剂量,改善这些复杂患者的治疗选择.
科学领域:
- 药理学 药理学是指药理学的学科.
- 腎臟病學 (nephrology) 是一種醫學.
- 内分泌学 在内分泌学.
背景情况:
- 慢性病 (CKD) 通过改变药物的药理动力学来复杂化糖尿病管理.
- 对脏药物清除的准确建模对于在患有CKD的糖尿病患者中安全有效的药物治疗至关重要.
- 为制药动力学 (PK) 建模收集大型临床数据集是资源密集的.
研究的目的:
- 开发一种灵活和数据效率高的方法,将受损清除纳入PK模型.
- 在CKD的背景下估计和模拟甲胺 (MET) 和达帕格利弗洛辛 (DAPA) 的药物清除.
- 为了指导在不同程度功能障碍的糖尿病患者中对MET和DAPA的剂量调整.
主要方法:
- 使用描述性统计和二次数据与机械PK模型和第一原则.
- 基于功能障碍的药物清除机制的生成概率密度函数.
- 估计的MET和DAPA的总清除,与其各自的PK模型进行模拟.
主要成果:
- 甲福明的清除与估计的球过率 (eGFR) 和净管道运输相成比例下降.
- 达帕格利弗洛辛的总清除与功能障碍的变化很小,随着非脏清除率的下降而下降.
- 估计的清除值和趋势与两种药物的已建立的PK文献保持一致.
- 模拟表明,基于估计清除量的剂量调整可以保持所需的药物暴露.
结论:
- 拟议的建模方法有效地纳入了患有CKD的糖尿病患者脏清理受损的情况.
- 这种方法提高了使用有限数据的PK建模的准确性,支持知情的治疗选择.
- 这些发现有助于在CKD患者中优化甲福明和达帕格利弗洛辛的剂量策略.
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