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Hi!
I have come across some data, where a compound was administered in
different regions of the GI track of rats: duodenum, jejunum, and ileum.
Same dose was given via cannulation in either region (3-4 rats per
region).
For both AUC and Cmax the results are: jejunum > duodenum > ileum. I
have some difficulties to understand why the values for jejunum are
larger than duodenum. Administering the drug in duodenum would mean
absorption from all the three parts of the GI track, whereas
administration of the compound in jejunum means that only jejunum and
ileum are involved in drug absorption. So why the Cmax and AUC are not
larger for duodenum compared to jejunum?
Assuming that jejunum is the most optimal site of absorption for this
compound, I can (to some extent) understand why Cmax values are bigger
after administration in this section: larger local concentration means
higher Cmax, whereas when the compound is administered in duodenum,
local concentrations in jejunum are lower by the time the drugs get
there. But what is the reason for larger AUC? Administering the drug in
duodenum should have 2 advantages compared to putting it in jejunum:
longer transit time and larger total surface.
Thank you!
Toufigh Gordi
Dear Toufigh,Back to the Top
some of the factors that have influenced the experimental outcomes:
1. the location of the drug "absorption window" in the GI tract (and
inter-regional differences in the drug absorption)
2. stability of the drug in the GI lumen at different regions
(degradation by enzymes, pH sensitivity, etc)
3. kinetics of transit of the intestinal contents through the different
regions
4. the first-pass metabolism (different % of the absorbed drug may be
metabolized if this process is saturable; direct infusion at the site
of absorption may result in this case in lower % degraded compared to
the infusion to the upper parts of the GI tract that may provide a more
gradual input of the drug to the absorption site)
For your drug the absorption in the different regions seems to be
similar to the general trend: jejunum > duodenum > ileum. The
experimental results may be explained by partial degradation of the
drug in the GI tract, or the first-pass metabolism, but other scenarios
are also possible.
Best regards,
David Stepensky
Weizmann Institute
Rehovot, Israel
e-mail: david.stepensky.-at-.weizmann.ac.il
Hi Toufigh,Back to the Top
You may need to check the physicochemical characteristics of your
compound.
If a compound is destroyed or precipitated
in the duodenum, you could see lower AUC and Cmax in duodenum than
jejunum.
I hope this proves helpful.
Joseph Kim
Clinical Pharmacokineticist
CPK/Modelling & Simulation
GlaxoSmithKline
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)