Delivery of fenoterol via Respimat, a novel 'soft mist' inhaler. a randomised, double-blind (within device), placebo-controlled, cross-over, dose-ranging study in asthmatic patients.
BACKGROUND
The phase-out of chlorofluorocarbons (CFCs) for metered dose inhalers (MDIs) has prompted the development of alternative propellants and the design of propellant-free devices for inhalation therapy.


OBJECTIVE
This study was carried out to determine the dose of fenoterol inhaled from Respimat (RMT), a new propellant-free soft mist inhaler, which is equivalent in terms of efficacy and safety to 1 puff of either 100 or 200 microg fenoterol inhaled from a conventional CFC-MDI (Berotec).


METHODS
Sixty-two asthmatic patients (35 male, 27 female) with a mean baseline FEV(1) of 1.7 liters, corresponding to 55% of the predicted normal value, were randomized at two study centers to 4 of a total of 8 possible treatments: placebo; 12.5, 25, 50, 100, or 200 microg fenoterol via RMT, and 100 or 200 microg fenoterol delivered via the MDI.


RESULTS
Fifty-nine patients completed the study as planned. Results of the therapeutic equivalence test for the primary endpoint, average FEV(1) (AUC(0-6))/6 and for the secondary endpoint, peak FEV(1), showed that the 12.5- and 25-microg fenoterol doses administered via RMT were equivalent to the 100 microg fenoterol dose from the MDI. The 50-, 100- and 200-microg fenoterol doses delivered by RMT did not meet the criterion for therapeutic equivalence with the 100-microg dose from the MDI, and if tested for a difference would have been significantly different in favor of RMT. All 5 RMT fenoterol doses were therapeutically equivalent to the MDI 200-microg fenoterol dose. Headache, reported by 4 patients on test days and 2 patients between test days in those randomized to RMT, was the most common adverse event, but the active treatments were generally well tolerated with no dose-dependent increases in incidence or severity of adverse events observed.


CONCLUSIONS
The results from the study suggest that safe and efficacious bronchodilation can be obtained from single-dose fenoterol administered via RMT. Use of lower absolute doses to obtain a clinically significant improvement in pulmonary function may be possible because of the increased lung deposition achievable with the novel soft mist inhaler.
van Noord
J A
JA
Department of Respiratory Diseases, Atrium Medical Centre, Heerlen, The Netherlands.
Smeets
J J
JJ
Creemers
J P
JP
Greefhorst
L P
LP
Dewberry
H
H
Cornelissen
P J
PJ
D000328:Adult; D000335:Aerosol Propellants; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D005617:Chlorofluorocarbons, Methane; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004867:Equipment Design; D005260:Female; D005280:Fenoterol / Q000008:administration & dosage*; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D013997:Time Factors; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects*
D000335:Aerosol Propellants; D001993:Bronchodilator Agents; D005617:Chlorofluorocarbons, Methane; D005280:Fenoterol