title: Efficacy response of inhaled HFA-albuterol delivered via the breath-actuated Autohaler inhalation device is comparable to dose in patients with asthma.
abstract: Handling difficulties, such as poor coordination of actuation and inhalation, are common in patients using press and breathe (P&Bs) metered-dose inhalers to administer asthma medication. Although spacers can help overcome some difficulties, the cumbersome nature of these devices often detracts from their use for the administration of rescue medications, where portability is important. This randomized, placebo-controlled, multicenter, crossover study investigated the efficacy, dose-response and safety of HFA-albuterol delivered via a breath-actuated Autohaler inhalation device in comparison with the same medication delivered using a conventional P&B device. In total, 39 patients received six study treatments in a random sequence at clinic visits separated by 2-7 days: 2 puffs from a HFA-placebo Autohaler; 1, 2, or 4 puffs from a HFA-albuterol Autohaler; I or 2 puffs from a HFA-albuterol P&B. Both active inhalers delivered 90 microg albuterol base equivalent/actuation from the actuator. The change from baseline in forced expiratory volume in 1 s (FEV1) and the area under the FEV1 curve (FEV1 AUC) were significantly greater than placebo for all active treatment groups (p < or = 0.01) and were suggestive of a dose response for each inhaler. Examination of the pooled slope of the dose responses for the Autohaler and P&B using Finney's Parallel Line Bioassay Methodology found a highly statistically significant relationship indicating the equivalence of the two inhalers on both parameters (p < or = 0.002). The relative potency of the two inhalers was 0.8 (95% CI: 0.47, 1.46) for the mean change from baseline in FEV1 and 0.9 (95% CI, 0.56, 1.48) for the change from baseline in FEV1 AUC. There was also a trend toward an increase in the mean percentage change from baseline in FEV1 as the number of puffs increased for both inhalers. Furthermore, there were no significant differences between the treatment groups with regard to time to onset of bronchodilator effect and the duration of effect was significantly greater than placebo (p < or = 0.01) in each of the active groups. Adverse events were generally mild to moderate in nature and were of similar incidence (< or = 18% of patients) in each group. This study demonstrates a dose-response for HFA-albuterol on bronchodilation using both the Autohaler and P&B devices and illustrates that, in patients with good coordination of inhalation with actuation, the efficacy and safety of the two inhalers is similar at equivalent doses.
authors.affiliation: Pharmaceutical Research & Consulting, Dallas, Texas 75231, USA. ggross144@aol.com
authors.forename: Gary
authors.initials: G
authors.lastname: Gross
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cohen
authors.forename: Harold
authors.initials: H
authors.lastname: Guy
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants / Q000008:administration & dosage*; D000420:Albuterol / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage*; D008297:Male; D036501:Metered Dose Inhalers; D016896:Treatment Outcome; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D000420:Albuterol; D001993:Bronchodilator Agents; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons