Beta2‐adrenergic ligand racemic formoterol exhibits enantioselective disposition in blood and skeletal muscle of humans, and elicits myocellular PKA signaling at therapeutic inhaled doses

摘要: While studies have demonstrated substantial differences in beta2 -adrenergic agonist enantiomer pharmacology, enantioselective disposition of long-acting ligand racemic (rac)-formoterol blood is inadequately explored after inhaled therapy given analytical challenges. Furthermore, information on and partitioning skeletal muscle absent despite its promising data anabolism humans. Using a sensitive ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay, we determined (R,R)-formoterol (S,S)-formoterol plasma samples from 11 non-asthmatic men who had rac-formoterol at therapeutic doses (2 × 27 μg). Mean (SD) concentrations (R,R)- biopsies the vastus lateralis 1 hour inhalation formoterol were 31 (15) 45 (18) pg mL-1 for (S,S)-formoterol, respectively, plasma, 0.56 (0.32) 0.51 (0.29) mgwet wt -1 , muscle. Formoterol exhibited different (p < 0.0001). In mean log (R,R):(S,S)-formoterol ratio was lower than 0 [-0.17(0.07), p 0.0001], whereas muscle, slightly higher [0.04(0.07), 0.05]. Log related to fiber-type composition. induced an approximately two-fold increase p-PKASer/thr phosphorylation 0.01), indicating response. Collectively, these findings suggest that exhibits modest humans, which appear greater (R,R)-enantiomer may be dependent