The extrapulmonary effects of increasing doses of formoterol in patients with asthma.
OBJECTIVE
To assess the cardiovascular and metabolic responses to increasing doses of formoterol administered from a dry powder inhaler.


METHODS
Twenty patients with mild to moderate asthma were given 12, 24, 48 and 96 microg of formoterol or a matched placebo on separate days. The doses were administered using a randomised, cross-over, double-blind design. The effects on heart rate, blood pressure, electromechanical systole (QS2I), the electrocardiographic QTc interval, plasma potassium (K); blood glucose and FEV1 were assessed prior to, and for 9 h following each dose.


RESULTS
There was no difference between the maximum effects of formoterol 12 microg and placebo; the 24 microg dose significantly decreased plasma K (-0.2 mmol x l(-1)) and increased blood glucose (1.8 mmol x l(-1)) compared to placebo. The two highest doses affected most of the variables with the 96 microg dose being significantly different from placebo for all indices, heart rate (9 beats x min(-1)), systol BP (4 mmHg), diastolic BP (-3 mmHg), QS2I (-11 ms), QTc (17 ms), plasma K (-0.5 mmol x l(-1)) and blood glucose (2.6 mmol x l(-1)). All doses of formoterol increased FEV1.


CONCLUSIONS
Although there were dose-dependent effects on the extrapulmonary measurements, only the effects at the highest dose may be of clinical significance.
Burgess
C
C
Department of Medicine, Wellington School of Medicine, New Zealand. hbark@wnmeds.ac.nz
Ayson
M
M
Rajasingham
S
S
Crane
J
J
Della Cioppa
G
G
Till
M D
MD
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects*; D000328:Adult; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D001786:Blood Glucose / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D000068759:Formoterol Fumarate; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D001993:Bronchodilator Agents; D004983:Ethanolamines; D011188:Potassium; D000068759:Formoterol Fumarate