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基于生理学的药物动力学建模Efavirenz纳米颗粒:从动物模型到人类推断

Thalita Martins da Silva^1,2, Michelle Alvares Sarcinelli¹, Marcelo Henrique Cunha Chaves¹

¹Laboratory of Micro and Nanotechnology, Center for Technological Development in Health, FIOCRUZ, 4036 Brasil Avenue, 21040-361 Rio de Janeiro, Brazil.

|October 13, 2025

概括

使用生理学基础的药理动力学 (PBPK) 模型开发 efavirenz (EFV) 纳米晶体可以增强药物输送. 这种纳米技术方法优化了剂量以改善患者的治疗结果.

科学领域:

制药科学制药科学
纳米技术纳米技术
药理动力学药理动力学

背景情况:

通过湿和喷雾干燥生产的 Efavirenz (EFV) 纳米晶体显示了增强的溶解.
对于翻译预测,需要一种特定于配方的,基于生理学的药理动力学 (PBPK) 模型.

研究的目的:

通过整合固态表征,体外性能和临床前药理动力学,为EFV纳米晶体建立PBPK模型.
为了使EFV纳米晶体在人类中的性能能够进行翻译预测.

主要方法:

使用各种技术 (衍射,光谱,热,形态,粒子大小测定) 进行EFV纳米晶体的表征.
在小鼠体内溶解试验和体内药理动力学分析.
使用 GastroPlus 构建和验证鼠类 PBPK 模型,并采用产品颗粒大小分布 (P-PSD) 方法.

主要成果:

与未经加工的EFV相比,EFV纳米晶体表现出更高的溶解效率 (90.4%与52.6%) 和均的大小分布.
在体内研究证实了纳米晶体增加EFV暴露.
鼠类PBPK模型准确地预测了血概况,误差在可接受的2倍范围内.

结论:

对人体生理学的推断表明,350毫克EFV纳米晶剂量提供与600毫克即时释放片剂相比的暴露,吸收速度更快.
敏感性分析确定了颗粒大小和胆汁盐溶解度是EFV口服吸收的关键因素.
这项研究开创了EFV纳米晶体的机械PBPK/PBBM模型,支持剂量优化,并突出了纳米技术在药物开发中的作用.

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