0000000000614008
AUTHOR
Carl Gunnar Regårdh
Role of P‐glycoprotein‐mediated secretion in absorptive drug permeabiity: An approach using passive membrane permeability and affinity to P‐glycoprotein††Dedicated to Prof. B. C. Lippold on the occasion of his 60th birthday.
Abstract It has been shown in vivo and in vitro that P‐glycoprotein (P‐gp) may be able to influence the permeability of its substrates across biological membranes. However, the quantitative contribution of the secretion process mediated by P‐gp on the overall permeability of membranes has not been determined yet. In particular, observations need to be clarified in which substrates showing high affinity to P‐glycoprotein, e.g., verapamil, apparently do not seem to be greatly influenced by P‐gp in their permeability and consequently also with respect to their extent of GI‐absorption after oral administration, whereas weaker substrates of P‐gp, e.g., talinolol, have clearly shown P‐gp‐related …
Caco‐2 versus Caco‐2/HT29‐MTX Co‐cultured Cell Lines: Permeabilities Via Diffusion, Inside‐ and Outside‐Directed Carrier‐Mediated Transport
Abstract Purpose The objective of this study was a systematic characterization and evaluation of cell culture models based on mixtures of Caco‐2/HT29‐MTX co‐cultures for their use in screening for drug absorption and intestinal permeability in comparison to the properties of the respective mono‐cultures. Methods Co‐cultures of Caco‐2 cells (absorptive‐type) and HT29‐MTX cells (goblet‐type) were set up. Three different co‐cultures (initial seeding ratios Caco‐2/HT29‐MTX: 90/10, 70/30, and 50/50) were grown on permeable filter supports, and monolayers were used for permeability studies with model compounds for paracellular absorption (atenolol, furosemide, H334/75, mannitol, terbutaline), tra…