PILOT-STUDY OF BRONCHODILATOR RESPONSE TO INHALED ALBUTEROL DELIVEREDBY METERED-DOSE INHALER AND A NOVEL DRY POWDER INHALER

Background: The metered-dose inhaler is currently one of the most pres cribed methods of delivering drugs to the Lungs. In the United States, mast currently marketed metered dose inhalers use chlorofluorocarbons as the system propellant and require patient breath coordination. The se factors lead to the need for a delivery system that is independent of propellants and patient Coordination.Objective: To compare the magn itude and time course of bronchodilation between albuterol delivered b y 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 Re search Center. Twelve mild to moderate asthmatic patients 12 to 36 yea rs of age participated in this study that involved three treatments, e ach separated by three to eight days, consisting of 2 puffs (90 mu g/p uff) albuterol by Ventolin metered-dose inhaler, two inhalations (100 mu g/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 3 0 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 treatmen t. Endpoints were compared with analysis of variance. Results: Five pa tients (one metered-dose inhaler and four dry powder inhaler) did not respond with >15% FEV1 increase over baseline within 30 minutes. Meter ed-dose inhaler and dry powder inhaler mean FEV, results, respectively , for 11 and 8 responders were 15 minutes in onset, 202.9 and 185.4 mi nutes in duration, 24.8% and 25.1% maximum change, and 18.6 and 18.2 a rea-under-FEV1-bronchodilation-curve. Statistical analysis of all pati ents and responders-only revealed both active treatments to be differe nt from placebo (P =.0018), but not different from each other (P =.129 1). No safety endpoints were significantly different among all three t reatments (P >.10 for all safety endpoints). Conclusions:In this study , the dry powder inhaler safely and effectively delivered a commercial ly available albuterol sulfate powder (Rotacaps) into human lungs with bronchodilation comparable to Ventolin metered-dose inhaler.