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基于生理学的药物动力学建模和临床推断,用于皮洛卡尔在眼上的局部应用:一项综合性研究
Jiaying Lin1, Fengjiao Bu2, Dan Wu3
1Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, China.
Journal of pharmaceutical sciences
|June 10, 2024
概括
眼局部应用为眼部药物输送提供了一条可行的途径,显示皮洛卡在子中具有显著的肌肉效应. 一个基于生理学的药理动力学 (PBPK) 模型预测,与子相比,人类的眼睛度较低.
科学领域:
- 眼科医生 眼科 眼科
- 药理动力学 药理动力学
- 药物运输 药物运输 药物运输
背景情况:
- 眼部药物输送面临生物可用性和方便性方面的挑战.
- 眼局部应用是治疗慢性眼病的一个有希望的策略.
研究的目的:
- 评估眼局部给药用于眼部药物输送的可行性.
- 在子中进行皮洛卡的药理动力学和药理动力学研究.
- 开发和验证一种基于生理学的药理动力学 (PBPK) 模型,用于眼药物输送.
主要方法:
- 在眼皮局部应用和眼滴灌注后,对子中的皮洛卡尔的药理动力学和药理动力学研究.
- 开发一种新的PBPK模型,用于通过皮肤吸收和眼部排放.
- 从子PBPK模型推断到人类,使用药物特异性透性和人类生理参数.
主要成果:
- 皮洛卡的度在子虹膜 (18,724 ng/g在2小时) 和水性幽默 (1363 ng/mL在1小时) 中达到顶峰,在眼应用后.
- 在眼应用后4个小时观察到显著的肌肉效应,而在眼应用后3个小时观察到眼滴.
- PBPK模型合理地预测了眼睛暴露,表明人类的度比子低10倍.
结论:
- 眼局部给药是一种可行的眼部药物输送途径,具有持续的治疗效果.
- 开发的PBPK模型可以预测人类的眼睛药理动力学,有助于药物开发.
- 应用在眼上的药物可以通过角膜和膜通道到达眼球.
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