Preliminary Data from Phase II Studies with Respimat, a Propellant-Free Soft Mist Inhaler

Abstract

Inhalation is regarded as the most effective treatment for respiratory disorders. Boehringer Ingelheim (Ingelheim am Rhein, Germany) has developed Respimat, a soft mist inhaler that delivers a metered dose of drug solution as an aerosol with a high "fine particle fraction" approximately five times slower than aerosols from chlorofluorocarbon-driven metered dose inhalers (CFC-MDIs). These characteristics have led to improved drug deposition in the lungs. In scintigraphic studies using fenoterol and flunisolide, mean drug delivery to the lungs was 31.1 to 44.6% of the dose delivered using Respimat compared with less than 20% using a CFC-MDI. Clinical studies in asthmatic patients using inhaled fenoterol alone (Berotec; Boehringer Ingelheim) or combined with ipratropium bromide (Berodual; Boehringer Ingelheim) confirmed the hypothesis that lower doses administered using Respimat should produce bronchodilator effects similar to those obtained with standard doses administered via a CFC-MDI. For Berotec, 12.5 or 25 micrograms administered by Respimat was therapeutically equivalent to either 100 or 200 micrograms administered by a CFC-MDI. For Berodual, bronchodilatory effects of 25/10- or 50/20-microgram doses using Respimat tended to be close or slightly superior to those of 100/40 micrograms using a CFC-MDI. Safety profiles did not differ between Respimat and CFC-MDI administration in either trial. Patients with airway hyperreactivity who inhaled placebo or drug solutions containing different preservatives and stabilizers had low incidences of paradoxical bronchoconstriction or asymptomatic decreases in lung function, which were similar with Respimat and a CFC-MDI. Furthermore, facial deposition data suggest a low risk of untoward effects even in potential misuse situations. Thus, Respimat promises to be a valuable alternative to conventional CFC-MDIs, with the additional benefit of improved drug targeting to the lungs.