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Bronchopulmonary pharmacokinetics of (R)- salbutamol and (S)-salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses


Jacobson, GA and Raidal, S and Robson, K and Narkowicz, CK and Nichols, DS and Walters, EH, Bronchopulmonary pharmacokinetics of (R)- salbutamol and (S)-salbutamol enantiomers in pulmonary epithelial lining fluid and lung tissue of horses, British Journal of Clinical Pharmacology, 83, (7) pp. 1436-1445. ISSN 0306-5251 (2017) [Refereed Article]

Copyright Statement

© 2017 The British Pharmacological Society

DOI: doi:10.1111/bcp.13228


Aims: Salbutamol is usually administered as a racemic mixture but little is known about the enantioselectivity of salbutamol pharmacokinetics in the lung. This study was designed to investigate enantiomer concentrations in lung tissue after inhaled dosing.

Methods: Horses (n = 12) received racemic salbutamol 1000 μg via inhalation. Enantioselective ultra performance liquid chromatography–tandem mass spectrometry was used to determine salbutamol 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: Mean ± 95% confidence interval (CI) yield of PELF was 57 ± 10 mg. Initial mean ± 95%CI (R)- and (S)-salbutamol PELF concentrations were 389 ± 189 ng g–1 and 378 ± 177 ng g–1 respectively, and both reduced approximately 50% by 15 min. Mean ± 95%CI central lung levels of drug were higher than peripheral lung tissue for both (R)-salbutamol (875 ± 945 vs. 49.5 ± 12 ng g–1) and (S)-salbutamol (877 ± 955 vs. 50.9 ± 12 ng g–1) respectively. There was no evidence of enantioselectivity in PELF or central lung but minor (~2%) enantioselectivity was observed in the peripheral lung. Enantioselectivity was clearly evident in plasma with (S):(R) ratio of 1.25 and 1.14 for both area under the concentration–time curve (0–25 min) and Cmax respectively.

Conclusion: PELF sampling in horses offers sufficient yield allowing direct detection of drug and, combined with tissue sampling, is a valuable model to investigate bronchopulmonary pharmacokinetics. Salbutamol did not demonstrate enantioselectivity in PELF or central lung tissue uptake following acute dosing, however, enantioselective plasma concentrations were demonstrated, with minor enantioselectivity in the peripheral lung.

Item Details

Item Type:Refereed Article
Keywords:albuterol, asthma, chiral, pharmacokinetics, respiratory, stereochemistry
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:119582
Year Published:2017
Web of Science® Times Cited:9
Deposited By:Pharmacy
Deposited On:2017-08-02
Last Modified:2018-07-26

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