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 Type:	Refereed Article
Keywords:	albuterol salbutamol, partitioning, performance-enhancing substances, muscular atrophy, doping, pharmacokinetics
Research Division:	Medical and Health Sciences
Research Group:	Cardiorespiratory Medicine and Haematology
Research Field:	Cardiology (incl. Cardiovascular Diseases)
Objective Division:	Health
Objective Group:	Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:	Cardiovascular System and Diseases
Author:	Jacobson, GA (Dr Glenn Jacobson)
Author:	Yee, KC (Dr Kwang Yee)
Author:	Premilovac, D (Dr Dino Premilovac)
Author:	Rattigan, S (Professor Stephen Rattigan)
ID Code:	88838
Year Published:	2013
Web of Science® Times Cited:	9
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2014-02-18
Last Modified:	2017-12-05
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