Effect of single doses of S-salbutamol, R-salbutamol, racemic salbutamol, and placebo on the airway response to methacholine.
BACKGROUND
Commercially available salbutamol is a racemic mixture consisting of equal amounts of the two enantiomers, R-salbutamol and S-salbutamol, felt to be active and inert, respectively.


METHODS
A double blind, randomised, four way, crossover study was performed in 12 well controlled asthmatic subjects (forced expiratory volume in one second (FEV1) > 70% predicted, no beta 2 agonists for > or = 4 weeks). Subjects were studied on four days at intervals of 48 hours to seven days. FEV1 was assessed before and both FEV1 and methacholine PC20 were measured 20 and 180 minutes after a single dose of nebulised racemic salbutamol 2.5 mg, R-salbutamol 1.25 mg, S-salbutamol 1.25 mg, and placebo.


RESULTS
Equivalent bronchodilation was seen for both R-salbutamol and racemic salbutamol (mean (SE) 12.4 (3.1)% and 12.0 (3.0)%, respectively, at 20 minutes and 5.9 (2.9)% and 5.2 (2.2)% at 180 minutes). The increase in FEV1 of 5.2 (0.9)% at 20 minutes and the decline in FEV1 of 2.9 (2.1)% at 180 minutes after S-salbutamol were not significantly different from the placebo response. Compared with placebo the methacholine PC20 after R-salbutamol and racemic salbutamol improved by 3.3 (95% CI 2.5 to 4.1) and 3.4 (95% CI 2.6 to 4.2) doubling doses, respectively, at 20 minutes and 1.2 (95% CI 0.6 to 1.8) and 1.0 (95% CI 0.2 to 1.8) doubling doses at 180 minutes. S-salbutamol resulted in an improvement of 0.9 (95% CI 0.3 to 1.5) doubling doses at 20 minutes and no change at 180 minutes. Restlessness (n = 11) and increased pulse were seen 20 minutes after racemic and R-salbutamol but not S-salbutamol or placebo, and not at 180 minutes. There were no other adverse events.


CONCLUSIONS
A single dose of 1.25 mg nebulised R-salbutamol produced equivalent bronchoprotection, bronchodilation, restlessness, and tachycardia as did 2.5 mg of racemic salbutamol. S-salbutamol 1.25 mg had a weak bronchoprotective effect; this could be because of a small amount of contamination with R-salbutamol or because S-salbutamol is an intrinsically weak beta 2 receptor stimulant.
Cockcroft
D W
DW
Department of Medicine, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
Swystun
V A
VA
D000328:Adult; D017109:Akathisia, Drug-Induced; D000420:Albuterol / Q000737:chemistry / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000737:chemistry / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D011674:Pulse; D013237:Stereoisomerism
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D016210:Methacholine Chloride; D000420:Albuterol