使用体外测量数据开发皮肤吸收的生理学基础药物动力学模型的影响:IVIVE案例研究
Yanling Zhang1, James F Clarke2, Yuri Dancik2
1Certara Predictive Technologies, Certara, Sheffield, UK. yanling.zhang@certara.com.
The AAPS journal
|September 2, 2025
概括
这项研究开发了一种基于皮肤生理学的咖啡因药理学 (PBPK) 模型,以改善体外透测试 (IVPT) 的解释和体外到体内外推断. 经过验证的PBPK模型有助于预测皮肤度和定义皮肤用药物的生物等价性参数.
科学领域:
- 药物动力学和药物输送
- 药理学中的计算建模
- 皮肤透科学
背景情况:
- 在体外透测试 (IVPT) 面临着皮肤药物输送评估的变化性和统计能力的挑战.
- 皮肤生理学基础的药物动力学 (PBPK) 模型提供了一种机理方法来解释IVPT数据,并使体外到体内抽象.
- 准确的建模对于了解皮肤中的药物行为和优化产品开发至关重要.
研究的目的:
- 开发和验证咖啡因的皮肤PBPK模型.
- 通过结合配方特征和分析方法约束来提高PBPK模型的预测可靠性.
- 使用PBPK模型进行体外到体外抽取,并探索皮肤配方的虚拟生物等价性.
主要方法:
- 用最少的参数优化构建了咖啡因的自下而上的皮肤PBPK模型.
- 该模型整合了配方特性,测量了皮肤分区系数和预测的扩散系数.
- 模型与文献IVPT数据进行了验证,随后对用增强剂的药膏,乳液和凝进行了模拟.
主要成果:
- 与之前的代相比,皮肤PBPK模型的预测可靠性有所提高.
- 该模型成功模拟了各种配方的咖啡因透,包括水溶液,乳膏和乳液.
- 在体内皮肤度的预测用于含有烯糖醇的凝配方,这是透增强剂.
结论:
- 经过验证的皮肤PBPK模型提供了一个可靠的工具来解释IVPT数据,并将结果从体外推断到体外.
- 该模型支持探索虚拟生物等价性和定义皮肤产品开发的"安全空间".
- 这种机械模型方法为监管提交和优化皮肤药物产品设计提供了宝贵的见解.
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