(R,S)-Salbutamol plasma concentrations in severe asthma

Objective: Salbutamol is commonly delivered as a racemic mixture of pharmacologically active (R)-salbutamol and inactive (S)-salbutamol. This study investigated inactive (S)- and active (R)-salbutamol plasma levels and their relationship to dose in patients with severe asthma. Methods: Basic demographics, racemic-salbutamol dose in the preceding 24 h, lung function tests at baseline and 1 h, and a 10 mL plasma sample were obtained from subjects presenting to the Department of Emergency Medicine with acute asthma. Plasma determinations were carried out using an LC-MS assay with solid phase extraction. Results: All patients (n = 5) had detectable levels of drug in plasma with range of 0·9–7·7 and 4·7–27·4 ng/mL for (R)-salbutamol and (S)-salbutamol respectively. These were correlated to total racemic salbutamol dose. The range of the (S) : (R) ratio was 2·0–5·2, with (R)-salbutamol representing 16–33% of the total plasma concentration, which did not correlate with total salbutamol dose. Conclusion: Only a small fraction of total plasma salbutamol concentration was found to consist of active enantiomer in patients with an acute severe exacerbation of asthma actively undergoing treatment with racemic-salbutamol. As a result of the possible contribution of (S)-salbutamol to poor asthma control further enantioselective investigations are warranted in severe asthma.