Back to the Top
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!
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (firstname.lastname@example.org)