Safety and tolerability of high-dose formoterol (via Aerolizer ®) and salbutamol in patients with chronic obstructive pulmonary disease

To evaluate the safety and tolerability of high-dose formoterol and salbutamol in patients with chronic obstructive pulmonary disease (COPD). In this two-way crossover, double-blind, double-dummy study, 17 adults with mild-to-moderate COPD were randomized to receive either formoterol 24 μg (2×12 μg via Aerolizer ®), or salbutamol 600 μg (6×100 μg via metered-dose inhaler), and the appropriate double-dummy q.i.d. at 4-h intervals for 3 consecutive days (total daily dose: 96 and 2400 μg, respectively). After a 4–7-day washout period, patients were switched to the other treatment. Treatment with high-dose formoterol and salbutamol was equally well tolerated, with no reports of serious adverse events. Both agents were associated with decreased plasma potassium (mean minimum values: 3.4 and 3.3 mmol/l for formoterol and salbutamol, respectively; P=0.914), increased serum glucose (mean maximum values: 9.0 and 8.7 mmol/l, respectively; P=0.373), and small increases in mean QTc interval (mean maximum 439 ms with both treatments; P=0.813). No clinically relevant between-treatment differences in adverse events or laboratory values occurred. Both drugs improved lung function (mean maximum forced expiratory volume in 1 s [FEV 1] 2.6 l with both treatments; P=0.624), with the improvement being significantly greater with formoterol than with salbutamol on all 3 days of treatment (mean area under the curve [AUC](0–24 h) of FEV 1 formoterol vs. salbutamol on days 1–3, all P