基于群体药理动力学模型的IVIVC,包含活性代谢物动力学:适用于阿塞克洛芬雅克持续释放配方
Taehyung Kim1, Tae Hwan Kim2, Soyoung Shin3
1School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi 16419, South Korea.
International journal of pharmaceutics
|February 1, 2026
概括
这项研究开发了一种药理动力学模型,用于从持续释放配方的体外溶解数据中预测阿塞克洛芬雅和迪克洛芬雅的血水平. 这种方法有助于开发有效的持续释放药物产品.
科学领域:
- 药理动力学和药物新陈代谢
- 制药科学 制药科学
- 生物制药生物制药公司
背景情况:
- 开发持续释放 (SR) 配方需要可靠的方法来从体外数据中预测体内药物性能.
- 阿塞克洛菲纳克是一种转化为迪克洛菲纳克的前药物,需要同时对这两种化合物的药理动力学建模.
- 建立体外-体内相关性 (IVIVC) 对于高效的配方开发和监管批准至关重要.
研究的目的:
- 建立基于群体药理学 (Pop-PK) 模型的在体外-在体内相关性 (IVIVC) 对阿塞克洛芬克SR配方.
- 使用体外溶解数据预测阿塞克洛芬雅及其活性代谢物迪克洛芬雅的血度.
- 验证开发的IVIVC模型的预测能力.
主要方法:
- 准备和实验室溶解测试 (方法) 三种阿塞克洛芬SR配方 (200毫克) 的不同释放率.
- 在口服后,对 beagle 狗进行体内药理学研究 (n=4 个配方).
- 使用LC-MS/MS.同时量化阿塞克洛芬雅克和迪克洛芬雅克的血度.
- 开发一个包含配方依赖溶解,吸收和代谢物动态的Pop-PK模型.
- 在体外溶解速率与体内溶解速率的相关性,以确定A级IVIVC.
主要成果:
- Pop-PK模型成功地描述了所有配方中aceclofenac和diclofenac的血度-时间概况.
- 在体外和体外溶解率之间观察到强烈的对数相关性 (R2 = 0.96),表明了高可预测性.
- 外部验证表明,分别对阿塞克洛芬纳克和迪克洛芬纳克的Cmax (1.32%和1.50%) 和AUC (16.49%和2.39%) 的预测误差很低.
结论:
- 一个基于人群的药理动力学模型的IVIVC成功地建立了阿塞克洛芬克SR配方.
- 开发的模型从体外溶解数据准确地预测了母药及其活性代谢物的药理动力学.
- 这种方法为SR配方的开发提供了实际框架,特别是对于具有活性代谢物的药物.
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