Bronchoprotective and bronchodilator effects of single doses of (S)-salbutamol, (R)-salbutamol and racemic salbutamol in patients with bronchial asthma

Abstract

Objectives: The drug salbutamol is used as a 50: 50 racemic mixture of its two enantiomers, (R)- and (S)-salbutamol. Previous studies suggest that the (R)-enantiomer is active, and the (S)-enantiomer is either inert or may be responsible for adverse effects. The aim of the study was to measure the protection given against methacholine (MCh) and adenosine monophosphate (AMP) by (R)-, (S)- and rac-salbutamol and their bronchodilator effects.

Methods: A double-blind, placebo-controlled, four-way cross-over study was performed in subjects with mild to moderate asthma. There were three groups: AMP₃₀ (n = 10), MCh₃₀ (n = 13) and MCh₁₈₀ (n = 10). The groups received AMP or MCh challenges at either 30 min or 180 min after each of four pretreatments: 100 μg (S)-salbutamol, 100 μg (R)- salbutamol, 200 μg rac-salbutamol or placebo (normal saline), each administered via nebuliser. Spirometry was measured at 30, 60, 90, 120, 150 and 180 min in the MCh₁₈₀ group.

Results: (R)- and rac-salbutamol showed equivalent bronchoprotective effects at 30 min. PC₂₀AMP increased by 3.22 (1.86) and 3.41 (2.15) doubling doses (P < 0.001) and PC₂₀MCh increased by 2.86 (1.09) and 2.75 (0.89) (P < 0.001) respectively. (S)-salbutamol caused no equivalent effect. There was no significant effect at 180 min. No hyper-responsiveness occurred after treatment with (S)-salbutamol. The mean increase in forced expiratory volume in 1 s (FEV₁) was 12.4% (6.8%) with (R)- and 12.0% (7.7%) with rac-salbutamol at 90 min. No significant change in FEV₁ occurred with (S)-salbutamol.

Conclusions: These results confirm other recent findings that the bronchoprotective and bronchodilator effects of salbutamol are attributable to its (R)-enantiomer. No adverse effects were noted after single doses of (S)-salbutamol.