Single-isomer R-salbutamol is not superior to racemate regarding protection for bronchial hyperresponsiveness

Abstract 

Bronchial hyper-reactivity (BHR) has been suggested to follow cessation of regular medication with racemic salbutamol. This study aimed at investigating the effects from medication with R,S- and R-salbutamol on bronchial response to provocation with isocapnic hyperventilation of cold air (IHCA).

Twenty-six patients with mild to moderate asthma were enrolled in a double-blind, randomised, cross-over study. Bronchial response to provocation was measured before and after 1 week's medication. Doses of 0.63mg R-salbutamol or 1.25mg R/S-salbutamol were inhaled three times daily during medication-weeks and a wash-out week intervened. Tests were performed 6h after the last dose of test drug. Impulse oscillometry and forced expiratory volume during one second were methods used to identify bronchial response to provocation. Two patients withdrew from the investigation due to side-effects, one from R- the other from R,S-salbutamol.

Comparable resting bronchial conditions were indicated by differences in baseline lung function values of <2% between study days. No statistically significant medication-dependent differences in BHR could be demonstrated between treatment groups. However, 15 patients exhibited higher (P=0.03) post-treatment BHR after pure R-salbutamol than after R,S-salbutamol. Furthermore, plasma concentrations of R-salbutamol tended to be lower (P=0.08) after medication with R- than after R,S-salbutamol despite equal doses of R-salbutamol given during the two separate treatment periods. We also found that considerable amounts of S-salbutamol were retrieved in plasma after medication with pure R-salbutamol.

We conclude that we were unable to demonstrate favourable effects of R-salbutamol over R,S-salbutamol regarding response to provocation with IHCA after regular medication of 1 week's duration.

Keywords:  Bronchial hyperresponsiveness, Salbutamol, Enantiomer, Asthma, IOS