Relative systemic dose potency and tolerability of inhaled formoterol and salbutamol in healthy subjects and asthmatics.
OBJECTIVE
To compare the relative systemic dose potency and tolerability of inhaled formoterol and salbutamol and to describe elimination of formoterol, particularly any enantioselectivity.


METHODS
Twelve healthy subjects, aged 18-28 years, completed three open study days, and eleven asthmatic patients, aged 20-56 years, completed four double-blind study days in randomised, placebo-controlled and crossover fashions. The healthy subjects inhaled 13.5 + 13.5 + 27 microg formoterol (Oxis) via Turbuhaler and 300 + 300 + 600 microg salbutamol (Ventoline) via a pressurised metered dose inhaler (pMDI). The asthmatics, being on formoterol 9 microg twice daily via Turbuhaler during the study, inhaled the same single doses as the healthy subjects plus 900 + 900 + 1800 microg salbutamol via pMDI. Doses were given cumulatively 30 min apart on separate study days. Placebo was a day of no treatment in the healthy subjects. Double dummies were used for the asthmatics. Cardiovascular and metabolic effects were evaluated. Elimination of formoterol was addressed in the healthy subjects.


RESULTS
Formoterol was estimated to be 28-109 times as potent as salbutamol, depending on the systemic effect variable. The duration of systemic action seemed to differ marginally at approximately equieffective doses of formoterol and salbutamol. Systemic effects were well tolerated and tended to be more pronounced in the healthy subjects than in the asthmatic patients. The half-life of the pharmacologically more active (R;R)-formoterol was longer than that of (S;S)-formoterol.


CONCLUSIONS
Systemically, formoterol was shown to be 28-109 times as potent as salbutamol. Equieffective doses seemed to have a similar duration of effect. Formoterol and salbutamol were well tolerated by healthy subjects up to the tested total doses of 54 microg and 1200 microg, respectively, and by asthmatic patients up to the tested total doses of 54 microg and 3600 microg, respectively. Elimination of formoterol was enantioselective.
Rosenborg
J
J
Experimental Medicine, AstraZeneca R&D Lund, Sweden. Johan.Rosenborg@astrazeneca.com
Bengtsson
T
T
Larsson
P
P
Blomgren
A
A
Persson
G
G
Lötvall
J
J
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068759:Formoterol Fumarate; D006207:Half-Life; D006801:Humans; D007773:Lactates / Q000097:blood; D008875:Middle Aged; D011188:Potassium / Q000097:blood
D001786:Blood Glucose; D001993:Bronchodilator Agents; D004983:Ethanolamines; D007773:Lactates; D000420:Albuterol; D011188:Potassium; D000068759:Formoterol Fumarate