Onset of Action of Single Doses of Formoterol Administered via Turbuhaler in Patients with Stable COPD

Abstract

We studied 16 patients with stable COPD in a double blind, double dummy, placebo-controlled, within patient study to see if formoterol could be used as a rescue drug. We compared the of onset of bronchodilation obtained with formoterol 12 μg (metered dose corresponding to 9 μg delivered dose) and formoterol 24 μg (metered dose corresponding to 18 μg delivered dose), both delivered via Turbuhaler, with that of salbutamol 400 μg and salbutamol 800 μg delivered via pressurized metered-dose inhaler (pMDI). Patients inhaled single doses of placebo, formoterol and salbutamol on five separate days. FEV1was measured in baseline condition and 3, 6, 9, 12, 15, 18, 21, 24, 30, 40, 50, and 60 min after inhalation of each treatment. We examined two separate criteria for deciding if a response was greater than that expected by a random variation of the measurement: (1) a rise in FEV1of at least 15% from the baseline value; (2) an absolute increase in FEV1of at least 200 ml. Formoterol 12 μg (15.2 min; 95% CI 9.5–21.0) and formoterol 24 μg (15.1 min; 95% CI 8.9–21.2) caused a rise in FEV1of at least 15% from the baseline value almost rapidly as salbutamol 400 μg (13.6 min; 95% CI 7.1–20.1) and salbutamol 800 μg (14.5 min; 95% CI 7.1–21.9). No significant difference (P=0.982) in onset of action was seen between the four active treatments. According to Criterion 2, the mean time to 200 ml increase in FEV1was 11.1 min (95% CI: 7.0–15.2) after salbutamol 400 μg, 13.0 min (95% CI: 7.9–18.1) after salbutamol 800 μg, 14.7 min (95% CI: 7.1–22.4) after formoterol 12 μg, and 12.7 min (95% CI: 7.4–18.0) after formoterol 24 μg. Again, there was no significant difference (P= 0.817) between the four active treatments. Formoterol Turbuhaler 12 μg and 24 μg caused bronchodilation as rapidly as salbutamol 400 μg and 800 μg given via pMDI.