Background: The metered-dose inhaler is currently one of the most prescribed methods of delivering drugs to the lungs. In the United States, most currently marketed metered dose inhalers use chlorofluorocarbons as the system propellant and require patient breath coordination. These factors lead to the need for a delivery system that is independent of propellants and patient coordination.
Objective: To compare the magnitude and time course of bronchodilation between albuterol delivered by Ventolin metered dose inhaler and albuterol sulfate powder (Rotacaps) delivered by a novel dry powder inhaler that generates a respirable drug aerosol over a range of inspiratory flow rates.
Methods: A single-center, single-dose, randomized, placebo-controlled, partial-blind, 3-way crossover study was conducted in an outpatient asthma Clinical Research Center. Twelve mild to moderate asthmatic patients 12 to 36 years of age participated in this study that involved three treatments, each separated by three to eight days, consisting of 2 puffs (90 micrograms/puff) albuterol by Ventolin metered-dose inhaler, two inhalations (100 micrograms/puff) albuterol sulfate powder (Rotacaps) by dry powder inhaler, and two inhalations (12.5 mg/inhalation) lactose powder by dry powder inhaler. Spirometry, blood pressure, and heart rate were measured at 30 minutes, 15 minutes, and immediately before treatment and then at 15, 30, 45, 60, 90, 120, 180, 240, and 300 minutes after each treatment. Serum potassium and glucose, and electrocardiograms were measured at 30 minutes before, and 30, 60, 90, and 180 minutes after each treatment. Endpoints were compared with analysis of variance.
Results: Five patients (one metered-dose inhaler and four dry powder inhaler) did not respond with > 15% FEV1 increase over baseline within 30 minutes. Metered-dose inhaler and dry powder inhaler mean FEV1 results, respectively, for 11 and 8 responders were 15 minutes in onset, 202.9 and 185.4 minutes in duration, 24.8% and 25.1% maximum change, and 18.6 and 18.2 area-under-FEV1-bronchodilation-curve. Statistical analysis of all patients and responders-only revealed both active treatments to be different from placebo (P = .0018), but not different from each other (P = .1291). No safety endpoints were significantly different among all three treatments (P > .10 for all safety endpoints).
Conclusions: In this study, the dry powder inhaler safely and effectively delivered a commercially available albuterol sulfate powder (Rotacaps) into human lungs with bronchodilation comparable to Ventolin metered-dose inhaler.