ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

摘要

简介: 吸入药物在许多肺部疾病的治疗中很重要，但要达到治疗效果，它们必须在肺部作用部位达到非结合浓度，足以与其药效特性 (PD) 相互作用，并在整个过程中发挥药理作用。适当的给药间隔。因此，药代动力学 (PK)/PD 关系的评估对于预测其可能的治疗效果至关重要。

涵盖的领域：我们回顾了用于评估用于治疗肺部疾病的主要吸入药物类别的 PK/PD 关系的方法。

专家意见：在产生有关吸入药物的肺浓度数据并将其解释为诱导所需治疗作用的能力方面仍然存在很大困难。肺的结构复杂性、同时涉及的过程的多样性以及肺与药物之间的物理相互作用使得任何用于吸入药物给药设计的 PK/PD 方法都极具挑战性。新的方法/方法正在增加我们对吸入药物会发生什么的了解，但它们仍未准备好用于监管目的。因此，我们仍然必须依赖基于公理的血浆浓度，即它们反映了肺内沉积的程度和模式。