title: Drug permeability in 16HBE14o- airway cell layers correlates with absorption from the isolated perfused rat lung.
abstract: The permeability of the lung is critical in determining the disposition of inhaled drugs and the respiratory epithelium provides the main physical barrier to drug absorption. The 16HBE14o- human bronchial epithelial cell line has been developed recently as a model of the airway epithelium. In this study, the transport of 10 low molecular weight compounds was measured in the 16HBE14o- cell layers, with apical to basolateral (absorptive) apparent permeability coefficients (P(app)) ranging from 0.4 x 10(-6)cms(-1) for Tyr-D-Arg-Phe-Phe-NH(2) to 25.2x10(-6)cms(-1) for metoprolol. Permeability in 16HBE14o- cells was found to correlate with previously reported P(app) in Caco-2 cells and absorption rates in the isolated perfused rat lung (k(a,lung)) and the rat lung in vivo (k(a,in vivo)). Log linear relationships were established between P(app) in 16HBE14o- cells and P(app) in Caco-2 cells (r(2)=0.82), k(a,lung) (r(2)=0.78) and k(a,in vivo) (r(2)=0.68). The findings suggest that permeability in 16HBE14o- cells may be useful to predict the permeability of compounds in the lung, although no advantage of using the organ-specific cell line 16HBE14o- compared to Caco-2 cells was found in this study.
authors.affiliation: King's College London, Pharmaceutical Science Research Division, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Fergus
authors.initials: F
authors.lastname: Manford
authors.forename: Ann
authors.initials: A
authors.lastname: Tronde
authors.forename: Ann-Britt
authors.initials: AB
authors.lastname: Jeppsson
authors.forename: Nilesh
authors.initials: N
authors.lastname: Patel
authors.forename: Fredrik
authors.initials: F
authors.lastname: Johansson
authors.forename: Ben
authors.initials: B
authors.lastname: Forbes
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001262:Atenolol / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D002460:Cell Line; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008790:Metoprolol / Q000493:pharmacokinetics*; D010539:Permeability; D051381:Rats
chemical_list: D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D008790:Metoprolol