Increase in Papp with concentration?

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Adam B Shapiro

One reason could be that the recovery of the compound increases as the concentration increases. Compound can be lost due to adsorption to surfaces, and since this is saturable, increasing the compound concentration can improve recovery.

Another reason could be an effect of the compound concentration on the rate of transport by P-glycoprotein.

If the compound is toxic to the cells and the monolayer is disrupted, that might enhance the rate of diffusion of the compound, with the toxic effect being greater at higher compound concentrations.

Miguel A Faria

Thanks for your answer.

I've tested the toxicity of the compounds and it showed to be negative in all the concentrations. The adsorption to plastic ware is also improbable as the compounds are highly hydrophilic. The effect of concentration increase is membrane transporters is probably the reason. Do you think P-gp can be involved in the transport of hydrophilic substances from cells to circulation? Thanks again.

Best

P-gp has the ability to recognize many different compounds as substrates for transport, although they usually are at least somewhat lipophilic. What is the calculated logP or logD of your compound?