Simplified administration of aerosolized drugs to small animals using metered dose inhalers

Animal studies involving administration of aerosolized drugs are complicated by the difficulties of generating and delivering the aerosol to the lungs effectively and reproducibly. A method utilizing a metered dose inhaler (MDI) would allow simplification and standardization of aerosol dosing. 18 adult BN rats were sensitized to ragweed. A spacer chamber was modified with a latex face mask that allowed insertion of an awake rat's nose and mouth into the chamber opposite the MDI. After MDI actuation, rats breathed either placebo or fluticasone 220 aerosol from the chamber for 60s, once daily X7d prior to and 1d after aerosolized ragweed challenge. Others were treated with s.c. dexamethasone X3d for comparison. Body and thymus weights were indicators of systemic steroid effect, and lung volumes, forced expiratory maneuvers and BAL cells were indicators of pulmonary allergic responses at 48h after allergen challenge. Fluticasone MDI treatment caused body weight loss and thymus weight loss compared with placebo treatment, indicating sufficient pulmonary delivery to obtain systemic effects. Body weight loss was greater with systemic dexamethasone treatment. Fluticasone also protected the rats from pulmonary allergic responses, with preservation of total lung capacity, FEV 0.2 and FVC, and reduced BAL inflammatory cells, compared with placebo treatment (p