估计参数,如肺部药物处置和沉积剂量,以及确定肺部药代动力学(PK)对药物疗效和安全性的影响,是开发吸入药物产品的关键因素,有助于更好地了解药物在肺部的命运。由于难以获得肺液,肺部的情况和PK仍然知之甚少。与其他生物流体相比,比如等离子体,用于直接或替代测量肺中活性化合物及其代谢物的浓度。孤立的灌注肺模型(IPL)的使用变得越来越普遍,它被认为是增加对这一领域理解的有用工具,因为它提供了控制给药的可能性,并且更容易对灌注液和灌洗液进行采样。该模型还提供了研究PK和药效学之间关系的机会。这篇综述描述了IPL模型的基本原理,如准备和建立方法,物种选择,药物管理,和肺活力调查。此外,IPL模型的不同应用,如药效学研究,药代动力学参数研究,如吸收,分布,和新陈代谢,和评价吸入制剂也进行了审查。
Estimating parameters such as pulmonary drug disposition and deposited dose, as well as determining the influence of pulmonary pharmacokinetics (PK) on drug efficacy and safety, are critical factors for the development of inhaled drug products and help to achieve a better understanding of the drugs\' fate in the lungs. Pulmonary disposition and PK have remained poorly understood due to the difficulty to access pulmonary fluids, compared to other biological fluids, such as plasma, for direct or surrogate measurement of the concentration of the active compounds and their metabolites in the lung. The use of the isolated perfused lung model (IPL) has become more common, and it is considered a useful tool to increase understanding in this area since it offers the possibility of controlling the administration and easier sampling of perfusate and lavage fluid. The model also provides an opportunity to study the relationship between PK and pharmacodynamics. This review describes the fundamentals of the IPL model, such as preparation and setting up the method, species selection, drug administration, and lung viability investigation. Besides, different applications of the IPL model like pharmacodynamic studies, pharmacokinetic parameters studies such as absorption, distribution, and metabolism, and evaluation of inhaled formulation have also been reviewed.