Cockcroft D W, Swystun V A
Department of Medicine, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
Thorax. 1997 Oct;52(10):845-8. doi: 10.1136/thx.52.10.845.
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.
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.
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.
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.
市售沙丁胺醇是一种消旋混合物，由等量的两种对映体R - 沙丁胺醇和S - 沙丁胺醇组成，分别被认为是活性和惰性的。
对12名病情控制良好的哮喘患者（一秒用力呼气量（FEV1）>预测值的70%，≥4周未使用β2激动剂）进行了一项双盲、随机、四路交叉研究。受试者在间隔48小时至7天的4天内接受研究。在单次雾化吸入2.5mg消旋沙丁胺醇、1.25mg R - 沙丁胺醇、1.25mg S - 沙丁胺醇和安慰剂之前以及之后20分钟和180分钟测量FEV1，在给药后20分钟和180分钟同时测量FEV1和乙酰甲胆碱PC20。
R - 沙丁胺醇和消旋沙丁胺醇均出现等效的支气管扩张（20分钟时，平均（SE）分别为12.4（3.1）%和12.0（3.0）%；180分钟时分别为5.9（2.9）%和5.2（2.2）%）。S - 沙丁胺醇给药后20分钟FEV1增加5.2（0.9）%，180分钟FEV1下降2.9（2.1）%，与安慰剂反应无显著差异。与安慰剂相比，R - 沙丁胺醇和消旋沙丁胺醇给药后20分钟乙酰甲胆碱PC20分别提高3.3（95%CI 2.5至4.1）和3.4（95%CI 2.6至4.2）倍剂量，180分钟时分别提高1.2（95%CI 0.6至1.8）和1.0（95%CI 0.2至1.8）倍剂量。S - 沙丁胺醇给药后20分钟提高0.9（95%CI 0.3至1.5）倍剂量，180分钟时无变化。消旋沙丁胺醇和R - 沙丁胺醇给药后20分钟出现躁动（n = 11）和脉搏加快，而S - 沙丁胺醇或安慰剂给药后未出现，180分钟时也未出现。未出现其他不良事件。
单次雾化吸入1.25mg R - 沙丁胺醇产生的支气管保护、支气管扩张、躁动和心动过速效果与2.5mg消旋沙丁胺醇相当。1.25mg S - 沙丁胺醇具有较弱的支气管保护作用；这可能是由于少量R - 沙丁胺醇污染，或者因为S - 沙丁胺醇本质上是一种较弱的β2受体激动剂。
