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对复杂的眼科悬浮液进行临床眼科暴露外推,使用基于生理学的药物动力学建模和模拟
Maxime Le Merdy1, Jessica Spires1, Ming-Liang Tan2
1Simulations Plus, Inc., 42505 10th Street West, Lancaster, CA 93534, USA.
Pharmaceutics
|July 27, 2024
概括
开发通用眼科药物是复杂的. 基于眼部生理学的药理动力学 (O-PBPK) 模型可以预测眼部药物暴露,有助于通用眼科产品的开发.
科学领域:
- 眼科医生 眼科 眼科
- 药理动力学 药理动力学
- 药物开发 药物开发
背景情况:
- 开发复杂配方的通用眼科药物存在重大挑战.
- 眼系统的复杂性和有限的测试方法阻碍了对药物生理相互作用的评估.
- 基于眼部生理学上的药理动力学 (O-PBPK) 模型为了解药物分布在难以进入的眼组织中提供了解决方案.
研究的目的:
- 证明O-PBPK模型在预测人类眼部药物暴露中的实用性.
- 用Besifloxacin (Bes) 眼科悬浮剂作为模型验证的案例研究.
- 评估模型在预测复杂眼科配方暴露方面的能力.
主要方法:
- 为Bes眼科悬浮剂开发了一个O-PBPK模型,包括鼻液排水,颗粒溶解和眼睛吸收/分布.
- 该模型考虑了控制释放配方 (Durasite®) 对药物保留的影响.
- 子眼部数据被用来验证模型,然后对生理参数进行调整,以推断人类.
主要成果:
- O-PBPK模型模拟准确地描述了子眼组织中观察到的Bes度.
- 该模型成功地预测了Bes在局部使用后在人眼中的暴露.
- 通过调整生理参数来实现对人类眼睛暴露的推断.
结论:
- O-PBPK模型是预测眼睛中药物暴露的宝贵工具,用于眼科仿制药开发.
- 这项研究验证了O-PBPK建模用于复杂的眼科悬浮剂的使用.
- 开发的模型有助于监管评估和开发通用眼科产品.
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