title: Safety and tolerability of high-dose formoterol (Aerolizer) and salbutamol (pMDI) in patients with mild/moderate, persistent asthma.
abstract: This double-blind, double-dummy, crossover study evaluated the tolerability of high-dose formoterol and salbutamol. Sixteen adults with mild/moderate persistent asthma (FEV1 > or = 70% predicted) were randomized to receive either formoterol 36 microg three times daily (TID) at 5-h intervals via Aerolizer (total daily dose 108 microg), or salbutamol 600 microg TID via pressurized metered-dose inhaler (total daily dose 1800 microg) for 3 consecutive days. After a 3-7-day washout period patients received the other treatment. FEV1 was measured 15 min pre-dose and 2 h post-dose. Both formoterol and salbutamol were associated with decreased plasma potassium (mean of minimum values: 3.4 and 3.6 mmol/L, respectively; P<0.001), increased serum glucose (mean of maximum values: 8.3 and 7.9 mmol/L, respectively; P=0.021), and small increases in mean QTc interval (mean of maximum values: 428.8 and 417.4 ms, respectively; P<0.001). However, none of these effects was clinically significant. Both treatments increased FEV1 to a mean maximum of 4.6 L (P=0.613), but the mean FEV1 AUC(0-72)h for formoterol was significantly greater than for salbutamol (302.2 L h, vs. 277.4 L h; P<0.001). No patients discontinued due to treatment-related adverse events. High-dose formoterol via Aerolizer did not produce any clinically significant systemic effects in patients with mild/moderate asthma.
authors.affiliation: PAREXEL International GmbH, Institute of Clinical Pharmacology, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kruse
authors.forename: Bernd
authors.initials: B
authors.lastname: Rosenkranz
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
mesh_terms: D000328:Adult; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000420:Albuterol; D000068759:Formoterol Fumarate