Drug permeability in 16HBE14o- airway cell layers correlates with absorption from the isolated perfused rat lung.
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.
Manford
Fergus
F
King's College London, Pharmaceutical Science Research Division, 150 Stamford Street, London SE1 9NH, UK.
Tronde
Ann
A
Jeppsson
Ann-Britt
AB
Patel
Nilesh
N
Johansson
Fredrik
F
Forbes
Ben
B
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
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D008790:Metoprolol