Salmeterol undergoes enantioselective bronchopulmonary distribution with receptor localisation a likely determinant of duration of action

Abstract

Background: Salmeterol (a long acting beta2-agonist) is a chiral molecule. (RR)-salmeterol is responsible for pharmacological effect, but basic knowledge of enantioselective pulmonary pharmacodynamics and pharmacokinetics of salmeterol remains unknown. There are safety concerns with (S)-enantiomers of beta2-agonists, with suggestions that these enantiomers may increase bronchial hyperresponsivneness in asthma patients. Methodology: Horses (n = 12) received racemic (rac-) salmeterol 250 μg via inhalation. Enantioselective UPLC–MS/MS was used to determine (R)- and (S)-salmeterol concentrations in pulmonary epithelial lining fluid (PELF) sampled 2, 5, 10 and 15 min after administration, in cent..