title: Safety and tolerability of high-dose formoterol (via Aerolizer) and salbutamol in patients with chronic obstructive pulmonary disease.
abstract: 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 microg (2 x 12 microg via Aerolizer), or salbutamol 600 microg (6 x 100 microg 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 microg, 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 1s [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<0.05). High-dose formoterol via Aerolizer (up to 96 microg/day) has a comparable tolerability profile to that of salbutamol in patients with mild-to-moderate COPD.
authors.affiliation: PAREXEL International GmbH, Klinikum Westend, Haus 18, Spandauer Damm 130, D-14050, Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Rosenkranz
authors.forename: Regine
authors.initials: R
authors.lastname: Rouzier
authors.forename: Matthias
authors.initials: M
authors.lastname: Kruse
authors.forename: Clair
authors.initials: C
authors.lastname: Dobson
authors.forename: Gareth
authors.initials: G
authors.lastname: Ayre
authors.forename: Ann
authors.initials: A
authors.lastname: Horowitz
authors.forename: Serge
authors.initials: S
authors.lastname: Fitoussi
mesh_terms: D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*
chemical_list: D001786:Blood Glucose; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000420:Albuterol; D011188:Potassium; D000068759:Formoterol Fumarate