Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation, The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) delivered via Respimat(R), a soft mist inhaler, and to establish the Respimat(R) dose which is as efficacious and as safe as the standard marketed dose of F/I(100140 mug) which is delivered via a conventional metered dose inhaler (MDI), In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 mug delivered via Respimat(R); F/I 50/20 or 100140 mug delivered via MDI, Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1 than placebo. A log-linear dose-response was obtained for the average increase in FEV1 up to 6 h (AUC(0-6) h) and peak FEV1 across the dose range administered by Respimat(R). Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat(R) compared with the MDI. However 12.5/5 and 25/10 mug F/I administered via Respimat(R) were closest (slightly superior) to the F/I dose of 100/40 mug delivered via MDI, Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat(R) compared to MDI, In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events, In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromide via Respimat(R), is as effective and as safe as higher doses given via a metered dose inhaler.
