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I wanted to determine the efflux mediated pathway of a drug. I had used
everted gut sac model. I have also validated this model in our lab by
conducting the studies using USFDA listed permeability model drugs (low
and high permeable drugs). High permeable drugs showed ~20 times higher
Papp values as compared to low permeable drugs (which is similar to the
observation reported using Caco-2 cell lines).
For determing the efflux-mediated absorption of the drug, I have
determined the Papp from both mucosal to serosal (M-S) and serosal to
mucosal side (S-M). The S-M permeation was higher in jejunum and ileum
as compared to M-S. The same study was repeated in the presence of a
known P-glycoprotein inhibitor (verapamil).
In this case M-S permeation was increased and S-M permeation was
decreased.
My queries are
1. Will these experimets be sufficient to declare the drug absorption
is mediated through P-gp
2. Do I need to use any other experimental model to confirm the result
3. What is the advantage of Ussing diffusion chamber model as compared
to everted sac model? Is there any difference in the tissue preapration
between both the models
4. Does Caco-2 cell lines give better result as compared to everted sac
model.
I will be happy to receive comments from all.
Regards
T. T. Mariappan
T. THANGA MARIAPPAN,
DEPT. OF PHARMACEUTICAL ANALYSIS,
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH (NIPER),
PHASE-10, SECTOR-67, MOHALI-160 062,
PUNJAB, INDIA
e.mail: ttmariappan.-a-.yahoo.co.in
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