对Levonorgestrel植入物体体内释放数据的基于模型的分析:预测长期系统性暴露
Soyoung Kim1, Brian Cicali1, Michelle Pressly1
1Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA.
Pharmaceutics
|May 27, 2023
概括
一个新的模型准确地预测了从皮下植入物中释放的勒沃诺格斯特勒 (LNG),这对于开发长效避孕药至关重要. 第一阶和位数模型最适合临床数据,有助于未来的配方开发.
科学领域:
- 药理动力学和药物输送方法
- 避孕技术开发 避孕技术开发
背景情况:
- 勒沃诺格斯特勒 (LNG) 是避孕药中的关键孕激素,但长效配方需要进一步开发.
- 研究释放功能对于优化液化天然气植入物配方至关重要.
研究的目的:
- 为皮下液化天然气植入物开发并将释放模型集成到基于生理学的药理动力学 (PBPK) 模型中.
- 用临床数据确定液化天然气植入物最准确的释放模型.
主要方法:
- 一个PBPK模型被调整为皮下液化天然气 (150毫克) 的管理.
- 探索了十个释放功能,以模仿液化天然气释放动力学.
- 使用临床试验数据 (n=537) 优化和验证释放参数和生物可用性.
主要成果:
- 第一阶和位数释放模型显示最适合观察到的数据 (调整后的R2分别为0.9170和0.9113).
- 这些模型预测,在0.0009/day.的速度下,负载剂量的最大释放量为~50%,最大释放率为0.0009/day.
- 综合PBPK模拟成功地回顾了观察到的血度.
结论:
- 一级和位数释放模型对于模拟皮下液化天然气植入物非常有价值.
- 开发的模型准确地捕捉了液化天然气释放动力学的中心趋势和变化.
- 未来的研究将将药物相互作用和BMI变异纳入模型.
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