(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.


CONCLUSIONS
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.
Jacobson
G A
GA
School of Pharmacy, University of Tasmania, GPO BOX 252-26, Hobart, Tasmania 7001, Australia. glenn.jacobson@utas.edu.au
Chong
F V
FV
Wood-Baker
R
R
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D010865:Pilot Projects; D013224:Status Asthmaticus / Q000097:blood*; D013237:Stereoisomerism
D001993:Bronchodilator Agents; D000420:Albuterol