开发适合年龄的结核病固定剂量组合,使用生理学基础的药动力学建模 (PBBM) 和风险评估
Xavier J H Pepin1, Juliana Johansson Soares Medeiros2, Livia Deris Prado2
1Simulations Plus, Inc., 42505 10th Street West, Lancaster, CA 93534-7059, USA.
Pharmaceutics
|January 8, 2025
概括
开发了一种新的生理基础生物制药模型 (PBBM),用于预测儿童的结核病药物暴露. 该模型证实了用于儿科的新型分散性片剂配方的安全性和有效性.
科学领域:
- 药物动力学和生物制药学
- 儿科药物开发 儿科药物开发
- 计算机建模 计算建模
背景情况:
- 结核病 (TB) 治疗维护依赖于异化 (INH) 和利芬素 (RIF).
- 巴西缺乏用于儿科结核病维持治疗的参考药物.
- 为所有儿科年龄组开发了一种新的适合年龄的INH和RIF可分散片剂配方.
研究的目的:
- 开发和验证一个基于生理学的生物制药模型 (PBBM) 来预测药物暴露.
- 为了将新的儿科结核病可分散片的体外性能与体内药业动力学 (PK) 数据联系起来.
- 评估新配方在儿童中的安全性和有效性.
主要方法:
- 利用INH和RIF的物理化学和生物制药特性.
- 在GastroPlusTM中开发了一种PBBM,它结合了机械代谢清除和配方分解/溶解数据.
- 模型验证使用文献和内部临床数据进行.
主要成果:
- PBBM成功地预测了不同年龄组和剂量方案的儿童的药物暴露.
- 有效性和安全性的概率模型与现实世界儿科数据相结合.
- 模型预测的全身暴露与临床结果相关.
结论:
- 开发的 PBBM 准确地预测了儿科结核病治疗的药理学特征.
- 新的可分散片剂配方和剂量方案预计对儿童来说是安全有效的.
- 这个模型支持在儿科药物开发中使用适合年龄的配方.
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