开发和验证用于PBPK建模的中国肥胖特异生理数据库
Ruwei Yang1, Yujie Wen1, Shengnan Zhang1
1Department of Pharmacy, The Third Xiangya Hospital, Central South University, 172 Tongzipo Road, Changsha, 410013, Hunan, China.
Clinical pharmacokinetics
|December 14, 2025
概括
这项研究为中国肥胖成年人开发了一种基于生理学的药理动力学 (PBPK) 种群模型. 新模型准确预测药物度,优于现有的东亚和白人肥胖人口模型.
科学领域:
- 药理动力学和药物新陈代谢
- 人口建模的人口建模
- 肥胖问题研究研究
背景情况:
- 基于生理学上的药理动力学 (PBPK) 模型对于预测特定人群中的药物行为至关重要.
- 现有的人口数据库可能无法准确地代表中国成年人和肥胖个体的独特生理特征.
研究的目的:
- 开发和验证针对中国肥胖人口量身定制的PBPK人口模型.
- 将这个新模型的预测准确度与现有的东亚和白人肥胖人口数据库进行比较.
主要方法:
- 在PK-Sim中建立了一个中国成年人口数据库,通过将东亚数据库与新的中国解剖和生理数据重新校准.
- 开发并验证了使用中国肥胖人口数据对德克塞梅托米丁,奥梅普拉和普罗波的PBPK模型.
- 通过调整基于中国患者数据和文献的生理参数,创建了一个中国肥胖成人数据库.
主要成果:
- 所有药物模型都得到了验证,预测的Cmax和AUC值在观察值的0.5-2倍之内.
- 与东亚数据库 (75%AUC,70%Cmax) 相比,中国成人数据库显示出更高的准确性 (90%AUC,80%Cmax在0.8-1.25倍范围内).
- 中国肥胖者数据库的表现明显优于白人肥胖者数据库 (83%AUC,33%Cmax与33%AUC,0%Cmax在0.8-1.25倍之间).
结论:
- 经过验证的PBPK模型和开发的中国成人和肥胖成人数据库可靠地预测这些人群中的药物度.
- 新的中国特有的模型为药物度预测提供了比现有的东亚和白人肥胖人口数据库更好的准确性.
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