Systemic and pulmonary effects of fluticasone administered through a metered-dose inhaler in rats.
BACKGROUND
Metered-dose inhalers (MDIs) are convenient, simple, inexpensive, and reproducible devices for administering aerosolized drugs through the pulmonary route, but methods have not been available for use of these devices in small animals.


OBJECTIVE
We sought to test the efficacy of delivery of fluticasone through an MDI to rats with a rodent-adapted spacer chamber and to compare this treatment with systemic dexamethasone for the acute pulmonary allergic inflammatory response.


METHODS
Changes in body and thymus weights were used as indicators for systemic steroid effects. Rats were sensitized to ragweed pollen extract 2 weeks before the experiment, and pulmonary allergic responses were evaluated 48 hours after a single aerosolized antigen challenge on the basis of bronchoalveolar leukocytes, lung tissue sections, total lung capacity, and forced expiratory volumes.


RESULTS
Inhaled fluticasone caused dose-related systemic effects, indicating successful pulmonary drug delivery. Inhaled fluticasone was more effective than placebo but less effective than systemic dexamethasone in attenuating the increase in lung eosinophils and inflammatory infiltrates and the decrease in total lung capacity associated with the allergic inflammatory response. Inhaled fluticasone prevented airway obstruction and proximal inflammation, as did dexamethasone, but it appeared to have less effect in areas of lung served by the most distal airways.


CONCLUSIONS
This is an effective method for use of MDIs to deliver inhaled drugs to small laboratory animals, and it should be valuable for investigations of treatment effects, as well as for in vivo testing of delivery devices.
Sorkness
Ronald L
RL
Morris Institute for Respiratory Research and the School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, WI 53705, USA. rlsorkne@wisc.edu
Remus
Jennifer L
JL
Rosenthal
Louis A
LA
D000730:Androstadienes / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D036501:Metered Dose Inhalers; D051381:Rats; D011914:Rats, Inbred BN; D014109:Total Lung Capacity / Q000187:drug effects; D014797:Vital Capacity / Q000187:drug effects
D000730:Androstadienes; D000068298:Fluticasone