Premium
Albuterol is net absorbed across human bronchial epithelial cell layers in an enantiomer‐dependent fashion
Author(s) -
Passante Egle,
Endter Sibylle,
Tindal Michael H,
Pankratz Michael R,
Frankish Neil H,
Ehrhardt Carsten
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1169-a
Subject(s) - enantiomer , chemistry , human lung , absorption (acoustics) , medicine , zoology , stereochemistry , lung , biology , materials science , composite material
Albuterol (ALB) and formoterol (FOR) two β 2 ‐adrenoceptor agonists are commonly used in the treatment of acute and chronic airway diseases. In this study, bi‐directional transport experiments of enantiomers of ALB (S‐ALB; R‐ALB) and FOR (S,S‐FOR; R,R‐FOR) across human bronchial epithelial cell (16HBE14o‐) layers were carried out. Both ALB enantiomers showed asymmetric fluxes, yielding a significant net absorption ( p > 0.05). Levalbuterol showed a more pronounced asymmetry than S‐ALB in absorptive P app values ( p = 0.06). P app of R‐ALB in the absorptive (AB) direction was 2.72±0.72×10 −6 cm/s, in comparison to 0.41±0.17×10 −6 cm/s in the secretive (BA) direction. P app values for S‐ALB were 1.81±0.44×10 −6 cm/s (AB) vs. 0.34±0.16×10 −6 cm/s (BA). For arformoterol a P app value of 3.69±0.57×10 −6 cm/s was measured in the AB direction and 3.83±0.27×10 −6 cm/s for the BA direction. S,S‐FOR exhibited an AB permeability of 4.02±1.68×10 −6 cm/s and a BA value of 4.59±0.63×10 −6 cm/s. Hence, the P app values of S,S‐FOR were neither significantly different from each other (i.e., AB vs. BA direction), nor from the values obtained for R,R‐FOR. The results of the presented study confirm our earlier results that ALB is actively absorbed across respiratory epithelial cells. A higher absorption rate was found for the (R)‐enantiomer compared to the (S)‐enantiomer. It can be further concluded that FOR is not a substrate for membrane transporters and crosses epithelial barriers in the lung by passive diffusion.