Fenoterol Delivery by Respimat® Soft Mist Inhaler Versus CFC Metered Dose Inhaler: Cumulative Dose-Response Study in Asthma Patients

Abstract

Objectives. Respimat® (RMT) soft mist inhaler (SMI) is a novel, propellant-free alternative to chlorofluorocarbon metered-dose inhalers (CFC-MDIs). The aim of this study was to evaluate the safety and establish the equipotent dose of fenoterol delivered by RMT SMI vs. a conventional MDI. Design. Double-blind, randomized, crossover, comparative study between fenoterol inhaled via RMT (either 50 µg/actuation, RMT50; or 100 µg/actuation, RMT100) and MDI (100 µg/actuation; MDI100). Patients and interventions. A total of 41 asthma patients received cumulative doses of fenoterol 600 µg (RMT50) or 1200 µg (RMT100 and MDI100) on 3 test days. Measurements and results. The bronchodilator response (forced expiratory volume in 1 second [FEV1]) was considered therapeutically equivalent (i.e., noninferior) if the 95% confidence intervals for the difference in their mean changes from baseline were within limits of ± 0.15 L. Systemic exposure was evaluated from plasma fenoterol levels. Adverse events (AEs) were recorded. RMT50 and RMT100 produced noninferior bronchodilatation to MDI100 from 30 minutes after the first dose. RMT50 showed equivalent safety and tolerability to MDI100, whereas RMT100 produced a higher incidence of AEs, a significantly greater plasma potassium reduction and a significant increase in pulse rate. Fenoterol plasma levels were twice as high with RMT100 as with RMT50 or MDI100. Conclusions. The nominal dose of fenoterol administered via RMT SMI can be at least halved to achieve equivalent efficacy, safety, and tolerability to a MDI.