Pourquoi et comment mesurer et optimiser le dépôt pulmonaire des traitements inhalés ?

The in vitro assessment of the aerosol fine particle 'respirable' fraction and the aerodynamic particle size distribution on cascade impactors is necessary to meet the demands of regulatory authorities but does not predict lung deposition of an inhaled drug notably in patients with chronic obstructive airway diseases. Total drug delivery to the lung can be assessed using pharmacokinetic methods. Pharmacokinetic studies are easier to conduct in patients with chronic obstructive diseases than imaging studies using two- or three-dimensional scintigraphic methods. For fast acting inhaled drugs, such as bronchodilators, the relationship between lung deposition and clinical efficacy can be established by modeling of the pharmacokinetic - pharmacodynamic (bronchodilation) relationship. Improvement of lung deposition is usually associated with a reduction of the dose required for clinical efficacy but the change in the dose-response relationship is not proportionally related to the increase in lung deposition. Aerosols delivering small particles improve lung deposition, by distributing drug diffusely throughout the lungs, in particular by reaching peripheral airways. These aerosols do not improve clinical efficacy as evaluated on classical spirometric or clinical criteria but often permit a reduction in dosage. Also, they can minimize oropharyngeal deposition, reduce variability in lung deposition and spirometric response related to change in inspiratory flows.