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


Jacobson, GA and Raidal, S and Robson, K and Narkowicz, CK and Nichols, DS and Walters, EH, Salmeterol undergoes enantioselective bronchopulmonary distribution with receptor localisation a likely determinant of duration of action, Journal of Pharmaceutical and Biomedical Analysis, 154 pp. 102-107. ISSN 0731-7085 (2018) [Refereed Article]

Copyright Statement

2018 Elsevier.

DOI: doi:10.1016/j.jpba.2018.02.048


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 central lung (endoscopic bronchial biopsy) and peripheral lung (percutaneous pulmonary biopsy) tissues (at 20 and 25 min respectively), and in plasma samples.

Results: Physiologically relevant tissue concentrations were found for both enantiomers, with median levels greater in central than peripheral lung (equivalent to 32 and 5 mM (R)-salmeterol for central and peripheral lung respectively). Levels in PELF decreased around 50% over 15 min and enantioselective distribution was observed in the central lung with levels of (R)-salmeterol around 30% higher than (S)-salmeterol.

Conclusion: Salmeterol distribution is enantioselective in the central lung. This suggests duration of action is more likely associated with specific B2ADR localisation effects rather than non-specific physiochemical factors which would not be enantioselective.

Item Details

Item Type:Refereed Article
Keywords:LABA, enantiomer, chiral, asthma, stereochemistry, respiratory, PK
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Pharmaceutical sciences
Objective Division:Health
Objective Group:Other health
Objective Field:Other health not elsewhere classified
UTAS Author:Jacobson, GA (Associate Professor Glenn Jacobson)
UTAS Author:Narkowicz, CK (Dr Christian Narkowicz)
UTAS Author:Nichols, DS (Dr David Nichols)
UTAS Author:Walters, EH (Professor Haydn Walters)
ID Code:124800
Year Published:2018
Web of Science® Times Cited:2
Deposited By:Pharmacy
Deposited On:2018-03-09
Last Modified:2019-09-09

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