The effect of formoterol over 24 h in patients with asthma: the role of enantiomers.
The single-dose effect of formoterol racemate and enantiomers on bronchodilatation up to 24 h was determined. Forty-six reversible asthmatic patients were randomised to this double blind, crossover study. Formoterol was inhaled by nebulizer (HaloLite); 4.5 and 36 microg of the racemate (rac-formoterol), 2.25 and 18 microg of (R;R)-formoterol, 18 mirog of (S;S)-formoterol, or placebo. Airway and systemic effects were assessed by serial measurements of forced expiratory volume during the first second, FEV1 (24 h), and heart rate (4 h). Rac- and (R;R)-formoterol significantly and dose-dependently increased FEV1 with similar mean maximal effect. (S;S)-formoterol was without significant effects on FEV1 and heart rate. (R;R)- and rac-formoterol were still effective 22-24 h after single high doses, but this was associated with some systemic side effect (increased heart rate) initially. Average 22-24 h FEV1 was 8% (rac-formoterol 36 microg) and 11% ((R;R)-formoterol 18 microg) over placebo, respectively. No significant differences in effects were observed between rac- and (R;R)-formoterol. Thus, the single dose bronchodilatating effect of formoterol resides in (R;R)-formoterol. This study does not indicate a clinically important advantage of (R;R)-formoterol as acute bronchodilator compared to the racemate.
Lötvall
Jan
J
The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, University of Göteborg, Sweden.
Palmqvist
Mona
M
Ankerst
Jaro
J
Persson
Gunnar
G
Rosenborg
Johan
J
Bengtsson
Thomas
T
Rott
Zsuzsanna
Z
Poczi
Magdolna
M
Devai
Agnes
A
Waldeck
Bertil
B
D000318:Adrenergic beta-Agonists / Q000737:chemistry / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology*; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D000068759:Formoterol Fumarate; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D013237:Stereoisomerism; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D000068759:Formoterol Fumarate