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Enantioselective disposition of (R/S)-albuterol in skeletal and cardiac muscle
Citation
Jacobson, GA and Yee, KC and Premilovac, D and Rattigan, S, Enantioselective disposition of (R/S)-albuterol in skeletal and cardiac muscle, Drug Testing and Analysis, 6, (6) pp. 563-567. ISSN 1942-7603 (2013) [Refereed Article]
Copyright Statement
Copyright 2013 John Wiley & Sons, Ltd.
DOI: doi:10.1002/dta.1575
Abstract
Significant enhancement of skeletal muscle function has been observed with racemic albuterol (salbutamol). There is now general
acceptance that the R-albuterol enantiomer elicits the pharmacological response, both in the lungs and extrapulmonary,
while S-albuterol is pharmacologically inert. The objective of this study was to investigate the distribution of (R/S)-albuterol
enantiomers into skeletal and cardiac muscle. Initially oral dosing was undertaken in neonatal mice administered a maximum
tolerable dose of racemic albuterol. An in vivo infusion rat model was employed for the investigation of albuterol uptake into
skeletal and cardiac muscle over 4 h. Tissue concentrations were determined using liquid chromatography-tandem mass spectrometry
(LC-MS/MS). From the oral dosing model, mean (±SD) levels of racemic albuterol after 5 days were 915 (±293) ng/mL
in plasma, 2574 (±196) ng/g in muscle, and 53 (±6.6) ng/g in brain with enantioselective partitioning (muscle:plasma ratio of
5.7 and 1.7 for R- and S-albuterol, respectively). In the infusion model, enantioselective disposition was observed in skeletal
muscle (muscle:plasma ratio of 1.2–1.7 and 0.6–0.7 for R- and S-albuterol, respectively) and in cardiac muscle (4.1 and 0.5, respectively).
In conclusion, there is greater partitioning of active (R)-albuterol than inactive (S)-albuterol into both skeletal and
cardiac muscle compared to plasma. These findings have relevance for albuterol sports doping, cardiac effects, and therapeutic
use in muscle wasting diseases. Furthermore, the greater muscle partitioning of the active R-albuterol, and the availability
of pure R-albuterol formulations highlight shortcomings in doping control measures using non-enantioselective assays.
Item Details
Item Type: | Refereed Article |
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Keywords: | albuterol salbutamol, partitioning, performance-enhancing substances, muscular atrophy, doping, pharmacokinetics |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Cardiovascular medicine and haematology |
Research Field: | Cardiology (incl. cardiovascular diseases) |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Jacobson, GA (Professor Glenn Jacobson) |
UTAS Author: | Yee, KC (Dr Kwang Yee) |
UTAS Author: | Premilovac, D (Dr Dino Premilovac) |
UTAS Author: | Rattigan, S (Professor Stephen Rattigan) |
ID Code: | 88838 |
Year Published: | 2013 |
Web of Science® Times Cited: | 14 |
Deposited By: | Menzies Institute for Medical Research |
Deposited On: | 2014-02-18 |
Last Modified: | 2017-12-05 |
Downloads: | 0 |
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