Open Access Repository

Beta2-adrenergic ligand racemic formoterol exhibits enantioselective disposition in blood and skeletal muscle of humans, and elicits myocellular protein kinase A-signalling at therapeutic inhaled doses

Downloads

Downloads per month over past year

Morton, H, Jacobson, G ORCID: 0000-0002-3409-8769, Narkowicz, CK, Habib, S, Nichols, DS ORCID: 0000-0002-8066-3132 and Jacobson, GA ORCID: 0000-0002-3409-8769 2019 , 'Beta2-adrenergic ligand racemic formoterol exhibits enantioselective disposition in blood and skeletal muscle of humans, and elicits myocellular protein kinase A-signalling at therapeutic inhaled doses' , Drug Testing and Analysis , doi: 10.1002/dta.2580.

[img] PDF
Hostrup_et_al-2...pdf | Document not available for request/download
Full text restricted until 5 March 2020.

Abstract

While studies have demonstrated substantial differences in beta2-adrenergic agonist enantiomer pharmacology, enantioselective disposition of long-acting beta2-adrenergic ligand racemic (rac)-formoterol in blood is unexplored after inhaled therapy given analytical challenges. Furthermore, information on enantioselective disposition and partitioning of beta2 -adrenergic agonist in skeletal muscle is absent despite its promising data on muscle anabolism in humans. Using a sensitive UPLC-MS/MS (ultra-high performance liquid chromatography-mass spectrometry) assay, we determined disposition of (R,R)-formoterol and (S,S)-formoterol in plasma and skeletal muscle samples from 11 non-asthmatic men who had inhaled rac-formoterol at therapeutic doses (2×27 μg). Mean (SD) concentrations of (R,R)- and (S,S)-formoterol in plasma and in muscle biopsies of the vastus lateralis 1 h after inhalation of formoterol were 31 (15) and 45 (18) pg×mL-1 for (R,R)-formoterol and (S,S)-formoterol, respectively, in plasma, and 0.56 (0.32) and 0.51 (0.29) pg×mgwet wt-1, respectively, in muscle. Formoterol exhibited different enantioselective disposition in plasma and muscle (p R,R):(S,S)-formoterol ratio was lower than 0 [-0.17(0.07), p R,R):(S,S)-formoterol ratio was slightly higher than 0 [0.04(0.07), p R,R):(S,S)-formoterol ratio in muscle was related to muscle fibre-type composition. Furthermore, formoterol induced an approximately two-fold increase in muscle p-PKASer/thr phosphorylation (p 2 -adrenergic response. Collectively, these findings suggest that formoterol exhibits modest enantioselective disposition in plasma after inhaled therapy in humans, which appear related to a greater (R,R)-enantiomer disposition in skeletal muscle that may be dependent on fibre-type composition.

Item Type: Article
Authors/Creators:Morton, H and Jacobson, G and Narkowicz, CK and Habib, S and Nichols, DS and Jacobson, GA
Keywords: beta2-agonist salbutamol muscle doping
Journal or Publication Title: Drug Testing and Analysis
Publisher: John Wiley & Sons
ISSN: 1942-7603
DOI / ID Number: 10.1002/dta.2580
Copyright Information:

© 2019 John Wiley & Sons, Ltd.

Related URLs:
Item Statistics: View statistics for this item

Actions (login required)

Item Control Page Item Control Page
TOP