新型抗生素开发的翻译PK/PD - - 药物开发者的视角
Caterina Bissantz1, Claudia Zampaloni2, Pascale David-Pierson1
1Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland.
Antibiotics (Basel, Switzerland)
|January 22, 2024
概括
新抗生素开发使用简化途径与非临床数据. 药理动力学/药理动力学 (PK/PD) 建模对于解释疗效至关重要,特别是对于具有新作用机制的新型抗生素.
科学领域:
- 药理学和制药科学 药理学和制药科学
- 传染性疾病 传染性疾病
- 药物开发 药物开发
背景情况:
- 传统的抗生素开发依赖于广泛的第三期临床试验.
- 监管机构现在允许简化新抗生素的开发途径,因为医疗需求尚未得到满足.
- 非临床数据,特别是翻译性药理动力学/药理动力学 (PK/PD) 研究,对于支持这些简化途径的疗效至关重要.
研究的目的:
- 在抗生素开发中审查经典PK/PD指数方法的价值和局限性.
- 探索具有新作用机制的新型抗生素的风险减轻策略.
- 为强大的药物开发提出一个全面的非临床PK/PD包.
主要方法:
- 讨论经典的PK/PD指数方法及其在监管指南中的应用.
- 分析与新型抗生素及其独特作用机制 (MoA) 相关的挑战.
- 引入基于半机制的PK/PD建模方法作为潜在的风险减轻策略.
主要成果:
- 经典的PK/PD指数方法对已知抗生素是有效的,但可能需要对新药进行增强.
- 翻译性PK/PD建模是支持简化抗生素开发的非临床包的关键组成部分.
- 额外的非临床研究和先进的PK/PD分析可以增加对新型抗生素疗效翻译的信心.
结论:
- 经典的PK/PD方法是基础性的,但可能不足以用于新型抗生素与新的MoAs.
- 基于半机制的PK/PD建模方法提供了一个有价值的风险减轻策略.
- 药物开发商应该将非临床PK/PD包量身定制为个人候选人,以获得强大的开发和监管批准.
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