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Could you please suggest any publications where p-gp's
involvement (excluding enterohepatic circulation or
biliary secretion) would cause a second peak in the
elimination phase of plasma-conc. profile due to
reabsorption of drugs from intestinal lumen?
A month ago, PharmPK had a good discussion about
explanation for a small second hump towards the last
time points after a single oral dose. I summarized all
the explanations, including: Enterohepatic
recirculation; Drug release from deep depot
compartment;Exsorption/secretion of drug and
subsequent reabsorption from the gut wall such as
P-gp; solubility-permeability tradeoff with pH for
ionized compounds and so on.
When I discussed the above explanations with a
colleague of mine, she said that there might be a
slight possibility of p-gp involvement but she
suspects its relevance in the actual systemic plasma
conc. profile. She further explained as follows: If
after the first absorption a drug is a P-gp substrate
and therefore efflux back into intestinal lumen, in
the second absorption pass it is at a lower
concentration than the first time, therefore less
likely to saturate P-gp, therefore more % of it gets
effluxed and less % get into circulation. It is
therefore highly unlikely to result in a double peak
by this mechanism.
I searched some databases by myself such as Pubmed and
didn't find any relevant information. Could anyone
give me some help on this? Really appreciate it!
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