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• W4229507206 abstract "Abstract Objectives The P-glycoprotein (P-gp) efflux pump is known to be present within several major physiological barriers including the brain, kidney, intestine and placenta. However, the function of P-gp in the airways of the lung is unclear. The purpose of this study was to use the highly specific P-gp inhibitor GF120918A to investigate the activity of the P-gp transporter in the airways to determine whether P-gp could influence inhaled drug disposition. Methods P-gp activity was measured as a change in digoxin transport in the presence of GF120918A in normal human bronchial epithelial (NHBE) cells, Calu-3 cell layers and the ex-vivo rat lung. Key findings The efflux ratios (ERs) in NHBE and Calu-3 cells were between 0.5 and 2, in contrast to 10.7 in the Caco-2 cell control. These low levels of GF120918A-sensitive polarised digoxin transport were measured in the absorptive direction in NHBE cells (ER = 0.5) and in the secretory direction in Calu-3 cells (ER = 2), but only after 21 days in culture for both cell systems and only in Calu-3 cells at passage &gt;50. The airspace to perfusate transfer kinetics of digoxin in the ex-vivo rat lung were unchanged in the presence of GF120918A. Conclusions These results demonstrated that although low levels of highly culture-dependent P-gp activity could be measured in cell-lines, these should not be interpreted to mean that P-gp is a major determinant of drug disposition in the airways of the lung." @default.
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• W4229507206 date "2009-03-01" @default.
• W4229507206 modified "2023-10-01" @default.
• W4229507206 title "In-vitro respiratory drug absorption models possess nominal functional P-glycoprotein activity" @default.
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• W4229507206 doi "https://doi.org/10.1211/jpp.61.03.0003" @default.
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