CLINICAL EQUIVALENCE OF A NOVEL NON-CHLOROFLUOROCARBON-CONTAINING SALBUTAMOL SULFATE METERED-DOSE INHALER AND A CONVENTIONAL CHLOROFLUOROCARBON INHALER IN PATIENTS WITH ASTHMA

Background: New formulations of non-chlorofluorocarbon-containing propellants for pressurized metered-dose inhaler delivery systems must be developed in response to the forthcoming ban on chlorofluorocarbon (CFC) production. Objective: This study compared the bronchodilator effects of 100, 200, and 300 mu g (base equivalent) of salbutamol in a novel CFC-free propellant system (Airomir in the 3M CFC-Free System; 3M Pharmaceuticals, St. Paul Minn.; 108 mu g of salbutamol sulfate or 90 mu g of salbutamol base equivalent per inhalation) with that of 100 and 200 mu g of salbutamol base in a conventional CFC propellant system (Ventolin, CFC-11/12; Allen and Hanburys, Division of Glaxo Inc., Research Triangle Park, N.C.; 90 mu g of salbutamol base per inhalation) and placebo. Methods: Twenty-six patients with chronic, stable asthma, who had a forced expiratory volume in 1 second (FEV(1)) between 50.0% and 75.0% of predicted normal value entered this randomized double-blind, double-dummy, 6-period, crossover study. FEV(1) was measured before and at multiple time points (ranging from 10 to 480 minutes) after administration of one, two, and three inhalations of salbutamol/CFC-free (100, 200, and 300 mu g); one and two inhalations of salbutamol/CFC (100 and 200 mu g); and placebo. Safety parameters included adverse events, heart rate, blood pressure, physical examinations, electrocardiograms, and clinical laboratory tests. Parametric analysis of variance models appropriate for a 6-period crossover design were used, along with multiple comparisons according to Tukey's method. Results: All active treatments produced significantly (p < 0.0001) greater bronchodilation than placebo. The bronchodilator effect, as measured by FEV(1) (peak percent change, peak as a percent of predicted value duration, and area under the curve) after two inhalations of salbutamol/CFC-free was clinically comparable to two inhalations of salbutamol/CFC, with no clinically meaningful differences in safety parameters between the two delivery systems or between different dose levels. Conclusion: These results suggest that salbutamol/CFC-free may offer a suitable alternative for salbutamol/CFC when the need arises to change front CFC-containing salbutamol products.