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The following message was posted to: PharmPK
Recently we ran a prodrug PO PK in rats with portal vein cannulation.
The orginal point of the experiment was to simply see if any intact
prodrug made it to the portal vein (there is none detected and yes,
we used esterase inhibitors in our collections).
We collected several time points over several hours. It is
interesting to me that even at time points past the known absorption
phase of the parent drug, concentrations in the portal vein are quite
a bit higher than in systemic circulation. May be this can be
attributed to recirculation followed by more liver metabolism.
At the risk of asking a very basic question, I am wondering if the
portal vein is truely considered part of the systemic circulatory
system or can it serve as a eddy/trap of sorts where drug can
concentrate momentarily after absorption (reabsorption).
If it is not right to consider the portal vein as part of the
systemic circulation, is there a volume correction I should use to
correct my calculated concentrations? It seems they could be
artifically high.
Does anyone know the volume in the portal vein of a rat comapred to
total volume or a reference with this type of information?
Thanks,
TFK
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The following message was posted to: PharmPK
Dear Tarra,
orally administered drug can undergo a variety of PK (or/and PD)
events following its absorption and until reaching the 'true'
systemic circulation in the 'peripheral' tissues (i.e., during its
way through the GI wall, portal circulation, and liver). Due to this,
the time course of the drug & metabolites concentrations in the
portal vein may be different from that in the 'peripheral' tissues.
In your case, portal vein concentrations of the active drug could be
higher than the systemic concentrations, for example, if metabolism
of the prodrug to the active drug takes place in the GI lumen or
wall, or in case of the enterohepatic circulation.
Regards,
David.
David Stepensky
HHMI Postdoc Associate
Department of Immunobiology
Yale University School of Medicine
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)