Collegues, in the Caco-2 drug permeability experiments (A to B) we have studied a drug and its new transport form and have found that drug's permeation through the cell membrane differs among these grups. In the case of new transport form group drug's concentration in the basal chamber (acceptor) rises much better than in the pure drug group. But when we have calculated Papp we have found no differences between those groups. Maybe somebody know why?
Hi Mikhail, if I recall correctly, Papp values are largely determined by the 'tightness' of the cell junctions. Permeability of your drug of interest however is likely determined by its transport not only through cell junctions but also through drug transporters and potentially other integral membrane protein channels. Therefore, it should not be surprising to see differences in the permeability of two different drug forms (due to transporter affinities/accessibility/etc) and no difference in Papp. In fact, since Papp is similar when testing the permeability of both drugs, it seems to indicate that the unique properties of each drug impact their individual transport rates across an epithelial layer.
Erik is correct about the routes for net permeability. One needs to establish the slow and high Papp of the system being used. There should not be more than 10-20% flux per time interval to ensure sink conditions, e.g., linear flux over time. Some cmpds can adversely affect the cell monolayer resulting in a upward curved cumulative flux with time. If a single time point is used, then this might appear similar to a linear profile.
- Badges
- Science topic
- Similar topics
- Biological Science
- Biochemistry
- Enzymology
- Enzymes