模拟肺输送器及其对吸入药物排放的影响
Shekhar Yeshwante1, Ramya Mahadevan2, Olagoke Sule1
1Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Pharmacological reviews
|November 26, 2025
概括
了解肺转运器是改善吸入药物输送模型的关键. 这次审查强调了它们对药理动学的影响,并呼吁更好地表征药物,以优化呼吸系统疾病的药物剂量.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 呼吸系统医学 呼吸系统医学
- 计算生物学 计算生物学
背景情况:
- 吸入药物输送为呼吸系统疾病提供了有针对性的治疗,提高了疗效,减少了全身副作用.
- 在呼吸道中准确的药理动力学 (PK) 评估具有挑战性,阻碍了最佳药物开发和剂量.
- 基于生理学上的药理动力学 (PBPK) 模型对于预测吸入药物暴露至关重要,但需要全面的输入数据.
研究的目的:
- 审查膜载体在人体呼吸道内吸入药物的处置中的作用.
- 解决有关肺输送体表达,定位及其对吸入药物PKs的影响的知识差距.
- 探索影响转运体表达的因素,包括疾病状态和炎症.
主要方法:
- 对肺输送物和吸入药物PK进行的临床前和临床研究的综合文献综述.
- 对人类肺部传送体表达,定位和变异性的现有数据的分析.
- 检查当前的PBPK建模方法及其对传送器数据的整合.
主要成果:
- 膜载体显著影响吸入药物排放,但它们在气道PK中的作用尚未完全理解.
- 关于输送体表达和在肺部的定位,存在相互矛盾的数据,疾病和炎症使其复杂化.
- 关于肺输送蛋白水平的有限量化数据,特别是在呼吸系统疾病中,限制了PBPK模型的增强.
结论:
- 彻底了解和量化肺输送器对于开发用于吸入治疗的强大的PBPK模型至关重要.
- 将传送器知识集成到PBPK模型中将改善肺部暴露的预测,并优化剂量策略.
- 需要进一步的研究来描述肺输送物及其在疾病中的动态变化,以推进吸入药物的开发.
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