Study objectives: To compare lung deposition of fenoterol or flunisolide administered from a novel, multidose inhalation device delivering liquid droplets (RESPIMAT; Boehringer Ingelheim Ltd; Bracknell, UK) or from conventional metered-dose inhalers (MDIs) with and without spacers.
Design: Two randomized, three-way crossover studies.
Setting: Clinical research laboratory.
Participants: Healthy, nonsmoking volunteers.
Interventions: In one study, radiolabeled aerosols of fenoterol from the RESPIMAT device and from a conventional MDI with or without an Aerochamber spacer (Trudell Medical; London, Ontario Canada). In the second study, radiolabeled aerosols of flunisolide from a RESPIMAT device, from a RESPIMAT device modified by inclusion of a baffle/impactor in the mouthpiece, and from a conventional MDI with an Inhacort spacer (Boehringer Ingelheim; Ingelheim, Germany).
Measurements and results: Assessment of the deposition of fenoterol or flunisolide in the lung and oropharynx using gamma scintigraphy. Safety was assessed based on reported adverse effects and spirometry ([FEV.sub.1] FVC, and peak expiratory flow rate) to detect any paradoxical bronchoconstriction. The RESPIMAT device delivered significantly more fenoterol to the lungs than either an MDI alone or an MDI with Aerochamber (39.2% vs 11.0% and 9.9% of metered dose, respectively; p [is less than] 0.01). Oropharyngeal deposition of fenoterol from the new device was lower than that from the MDI (37.1% vs 71.7%, respectively, p [is less than] 0.01). The RESPIMAT device deposited significantly more flunisolide in the lungs compared with MDI plus spacer (44.6% vs 26.4%, respectively; p [is less than] 0.01), while resulting in similar oropharyngeal deposition (26.2% vs 31.2%, respectively). Introduction of a baffle into the RESPIMAT system reduced lung deposition of flunisolide to 29.5%, and oropharyngeal deposition to 7.8% (p [is less than] 0.01).
Conclusion: The RESPIMAT device may prove to be an effective alternative to MDIs for the administration of inhaled bronchodilators and corticosteroids. The high lung deposition and low oropharyngeal deposition may lead to improved efficacy and tolerability of inhaled medications, especially corticosteroids. (CHEST 1998; 113:957-63)
Key words: flunisolide; fenoterol; gamma scintigraphy; inhaler devices; lung deposition; oropharyngeal deposition
Abbreviations: CFC=chlorofluorocarbon; MDI=metered-dose inhaler
Currently, most drugs used in the treatment of asthma and airflow obstruction are given by the inhaled route. This includes bronchodilators such as [[Beta].sub.2]-agonists and anti-cholinergics, and anti-inflammatory medications such as corticosteroids, cromolyn sodium, and nedocromil sodium. Inhaled medication is preferable to oral medication because the drug is delivered directly to the airways, allowing lower doses to be used, usually a more rapid onset of action, and a reduced incidence of side effects.[1,2] The pressurized metered-dose inhaler (MDI) is the most widely used inhaler device. It has the advantages of being compact, portable, relatively cheap, and easy to use. However, many patients, especially children and the elderly, do not obtain optimal benefit because they fail to use their MDIs effectively.[3-5]
Most conventional MDIs contain chlorofluorocarbon (CFC) propellants. However, CFCs are thought to contribute to ozone depletion in the atmosphere and from January 1996, the production of CFCs has become severely restricted in line with the Montreal Protocol. Therefore, alternative drug delivery systems for inhalation therapy are...