title: Lung deposition of HFA beclomethasone dipropionate in an animal model of bronchopulmonary dysplasia.
abstract: The best delivery of a drug in ventilated neonates is obtained when using a small particle diameter solution administered via a spacer. Lung deposition of hydrofluoroalkane beclomethasone dipropionate (QVAR, 1.3 microm particles), delivered via an Aerochamber-MV15, was measured in piglets under conditions mimicking ventilated severely ill neonates (uncuffed 2.5 mm endotracheal tube; peak pressure 16 cm H2O; respiratory rate 40/min). After determining the mass and particle size distribution of the 99mTc-labeled and unlabeled drug, three lung deposition studies were performed: after 1 h of ventilation (controls, n = 18), after 48 h aggressive ventilation inducing an acute lung injury (nine piglets out of the controls), and after increasing the pressure to 24 cm H2O during drug delivery (five piglets out of the nine with acute lung injury). All piglets were then killed for lung histology. Results (median, range), expressed as a percentage of the delivered dose, were compared using an inferential or the Friedman test. While lung deposition was low, it was greater (p = 0.003) in controls (2.66%, 0.50-7.70) than in piglets with histologically confirmed acute lung injury (0.26%, 0.06-1.28) or under a high-pressure ventilation (1.01%, 0.30-2.15). Lung deposition of QVAR in an animal model of ventilated neonates is low, variable, and dramatically affected by lung injury.
authors.affiliation: INSERM U-618, Université François-Rabelais, Tours, F-37000, France. jean-christophe.dubus@ap-hm.fr
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Dubus
authors.forename: Jérôme
authors.initials: J
authors.lastname: Montharu
authors.forename: Laurent
authors.initials: L
authors.lastname: Vecellio
authors.forename: Michèle
authors.initials: M
authors.lastname: De Monte
authors.forename: Anne
authors.initials: A
authors.lastname: De Muret
authors.forename: Arnaud
authors.initials: A
authors.lastname: Goucher
authors.forename: Sylvain
authors.initials: S
authors.lastname: Cantagrel
authors.forename: Alain
authors.initials: A
authors.lastname: Le Pape
authors.forename: Karen
authors.initials: K
authors.lastname: Mezzi
authors.forename: Caroline
authors.initials: C
authors.lastname: Majoral
authors.forename: Sandrine
authors.initials: S
authors.lastname: Le Guellec
authors.forename: Patrice
authors.initials: P
authors.lastname: Diot
mesh_terms: D000335:Aerosol Propellants; D000818:Animals; D000831:Animals, Newborn; D001507:Beclomethasone / Q000493:pharmacokinetics*; D001997:Bronchopulmonary Dysplasia / Q000378:metabolism*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000493:pharmacokinetics*; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism*; D008297:Male; D013552:Swine; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D001507:Beclomethasone; D005938:Glucocorticoids; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons