最小的生理学基础的药动力学建模,以预测在禁食和Fed状态下溶解不良的cinacalcet化物度-时间概况

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Updated: Jan 17, 2026

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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

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Xiaoqian Xie¹, Le Sun²

¹Department of Pharmaceutics, School of Pharmacy, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.

European journal of drug metabolism and pharmacokinetics

|January 15, 2026

概括

一个最小的生理学基础的药理动力学 (mPBPK) 模型准确地预测了禁食和食状态下的cinacalcet化物度. 该模型还为药物溶解概况建立了强烈的体内-体外相关性.

科学领域:

药理动力学和药物新陈代谢
计算机建模和模拟
制药科学制药科学

背景情况:

药代动力学 (PK) 曲线对于优化药物剂量,疗效和安全至关重要.
甲酸是溶解不良的药物,需要精确的PK评估.
预测模型有助于理解各种生理条件下的药物行为.

研究的目的:

开发一个最小的生理学基础的药理动力学 (mPBPK) 模型,用于cinacalcet化.
在禁食和食状态下预测药物度-时间概况.
为了确定甲酸的体内-体内溶解相关性.

主要方法:

整合一个六个组织区的mPBPK模型与一个隔间吸收和传输模型.
包括胃,七个小肠和大肠区,用约翰逊方程进行体内溶解计算.
在三个剂量级别中对模型的外部验证.

主要成果:

mPBPK模型显示出高精度和可靠性,外部验证的误差范围为两倍.
在禁食条件下,在体内和体外溶解资料之间建立了强烈的相关性 (R2 = 0.991).
该模型在预测禁食条件方面表现出优异的表现,与卷积和解卷积等传统方法相比.

结论:

该mPBPK模型准确地预测了在禁食和食状态下对cinacalcet化的血度-时间曲线.
这种建模方法提供了一种新的方法来确定体内-体外相关性.
该模型适用于各种类型的药物产品,包括释放不完全,持续释放或吸收差的药物产品.

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