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Dear all,
I want to add a third compartment (Gut) to a two compartmental model
due to enterohepatic recirculataion. can I assume the aborption rate
(from gut to central compartment) as first rate (Ka), while taking
the release process (from central compartment to gut) as a
discontinuous process? It is convinceable if this happens in dog
since dog has a gall. The question is, should I consider the bile
release as a discontinuous or continuous process? Any suggestions are
very well welcome. Thanks,
Cherry
[One compartment example at http://www.boomer.org/manual/EG/ehrc0/
ehrc.html - db]
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The following message was posted to: PharmPK
Cherry,
Modeling enterohepatic circulation is not as straightforward as your
example
- at least not when the species has a gall bladder.
In GastroPlus(tm), we use a model that consists of the following
mechanisms:
(1) Diversion of a fraction of total hepatic clearance to the bile duct
(biliary clearance, or fbc)
(2) Diversion of a fraction of this fbc to the gall bladder during
fasted
state (fgb), with the remainder (fbc-fgb) continuously recirculated
into the
duodenum.
(3) Emptying of the gall bladder begins at mealtime (switching to fed
state
model parameters), with a defined emptying time following a Gaussian
emptying function
(4) Gall bladder emptying stops when fasted state resumes (we
typically use
two hours in fed state, but you can vary this)
With this method, we are able to fit a single model parameter (the
biliary
clearance fraction) and explain multiple peaks in a variety of data
sets.
Note that proper modeling of enterohepatic circulation requires the
consideration of the differences in fasted and fed states, as well as
recognizing that Ka is not a constant, but is a coefficient that changes
significantly with time for the majority of drugs.
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (AMEX: SLP)
1220 W. Avenue J
Lancaster, CA 93534-2902
U.S.A.
http://www.simulations-plus.com
Phone: (661) 723-7723
FAX: (661) 723-5524
E-mail: walt.at.simulations-plus.com
[Walt, Gaussian emptying function? Starts slow, peaks and then
slower? Variable ka ? ;-) - db]
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)