| Popis: |
The use of nebulization is becoming increasingly frequent in treatment of acute or chronic lung diseases for delivery of topically active drugs and is also an attractive way to deliver systemic drugs. A nebulizer can be defined by the aerodynamic properties of the emitted particles which are directly related to the lung deposition and the clinical response to a nebulized drug. New guidelines elaborated by an European norm (ENFR13544-1) aim to participate to a better control on quality and efficiency of existing devices and inspired the elaboration of the studies of this thesis. The aim of these works was to evaluate the nebulization function of a new kind of modality, the intrapulmonary percussive ventilation which contrarily to classical jet nebulizers nebulizes drugs under superimposed percussion conditions. In vitro measurements were realized by cascade impaction and laser diffraction. Lung deposition was investigated by imagery techniques and pharmacokinetic study. Aerodynamic properties were different between the in vitro methods. When measured by cascade impaction, MMAD and FPF were smaller for IPV comparatively to SST. By laser diffraction, FPF remained lower but MMAD was higher with IPV than with SST. The effect of percussions was greater on MMAD than on FPF. An irregular intrapulmonary deposition and a higher whole body deposition due to a higher extrapulmonary deposition with the IPV were measured by scintigraphy. The pharmacokinetic study highlighted that the drug output and the lung dose were lower when amikacin was delivered by IPV comparatively to SST. All results of these different studies seem unfavourable to the use of intrapulmonary percussive ventilation as modality of administration for nebulized drugs without further investigations. Results presented in this thesis concerning exclusively healthy subjects, we hope that they encouraged to perform complementary analysis and observations in different conditions such as patients with lung disease. |
