Unit of Pharmacology, Dept. Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
Unit of Respiratory Disease and Lung Function, Dept. Medicine and Surgery, University of Parma, Parma, Italy.
Expert Opin Drug Deliv. 2021 Jul;18(7):891-906. doi: 10.1080/17425247.2021.1873271. Epub 2021 Jan 19.
: Inhaled drugs are important in the treatment of many lung pathologies, but to be therapeutically effective they must reach unbound concentrations at their effect site in the lung that are adequate to interact with their pharmacodynamic properties (PD) and exert the pharmacological action over an appropriate dosing interval. Therefore, the evaluation of pharmacokinetic (PK)/PD relationship is critical to predict their possible therapeutic effect.: We review the approaches used to assess the PK/PD relationship of the major classes of inhaled drugs that are prescribed to treat pulmonary pathologies.: There are still great difficulties in producing data on lung concentrations of inhaled drugs and interpreting them as to their ability to induce the desired therapeutic action. The structural complexity of the lungs, the multiplicity of processes involved simultaneously and the physical interactions between the lungs and drug make any PK/PD approach to drug delivery design for inhalation medications extremely challenging. New approaches/methods are increasing our understanding about what happens to inhaled drugs, but they are still not ready for regulatory purposes. Therefore, we must still rely on plasma concentrations based on the axiom that they reflect both the extent and the pattern of deposition within the lungs.
吸入式药物在许多肺部疾病的治疗中非常重要，但为了达到治疗效果，它们必须在肺部的效应部位达到游离浓度，该浓度足以与药效学特性（PD）相互作用，并在适当的给药间隔内发挥药理作用。因此，评估药代动力学（PK）/药效学（PD）关系对于预测其可能的治疗效果至关重要。
我们回顾了用于评估主要类别的吸入式药物的 PK/PD 关系的方法，这些药物被用于治疗肺部疾病。
在产生吸入式药物的肺部浓度数据并解释其诱导所需治疗作用的能力方面，仍然存在很大的困难。肺部的结构复杂性、同时涉及的多种过程以及肺部与药物之间的物理相互作用，使得任何针对吸入式药物的 PK/PD 方法都极具挑战性。新的方法/方法增加了我们对吸入式药物的了解，但它们仍不适用于监管目的。因此，我们仍然必须依靠基于这样一个公理的血浆浓度，即它们反映了肺部沉积的程度和模式。
