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Dear all,
We want to implement an in vitro test to predict the human intestinal
absoprtion of chemicals. Therefore I would like to know which is the
best method to use to obtain such data. What are your feelings about
the different methods currently in use :
Caco-2 cell monolayer model
MDCK
PAMPA model
HPLC with IAM columns
Finally, are ther new promising methods to predict HIA ?
Thanks for your comments
Fred
Frédéric Ooms, Ph.D.
Chemistry Project Manager
Euroscreen S.A.
Rue Adrienne Bolland 47
6041 Gosselies
Belgium
www.euroscreen.be
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Frederic,
All four the methods you mentioned are in use today with varying
support as well as varying degrees of success. the Caco-2 model has the
largest set of data, but many other methods are gaining in popularity.
One caveat is that the PAMPA and IAM column models to not take any
transport phenomenon into account. This could be important in the
evaluation of human intestinal absorption seeing as transporters play
an important role in the intestinal absorption of many compounds.
Another possibility is the various in silico models that are available.
Although these models are not as good as in vitro data, they do have
value in early discovery settings to prioritize compounds. Good luck in
your decision.
Nathan Teuscher
Nathan S. Teuscher, PhD.
Drug Metabolism Scientist
NPS Pharmaceuticals
420 Chipeta Way
Salt Lake City, UT 84108
Email: nteuscher.-at-.npsp.com
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The following message was posted to: PharmPK
Dear Frederic,
In my opinion it is very difficult to say which is the best method for
predicting human intestinal absorption of chemicals.
This would depend on at which point of drug discovery are we looking for
this information.If it is at a very early stage,for example around
screening
probably the information one gathers from HPLC with IAM columns would be
good enough.If it is around LI PAMPA would be a good system.This would
classify molecules into low,mmedium and high permeability classes and
would
account for molecules being absorbed by the passive transcellular
route.This
is the route by which most of the orally drugs administered are
absorbed.
But if we are looking for other modes of transport along with Efflux by
PGp
etc then a biological system would serve as a good model for prediction.
I think PAMPA would be a reliable model at the initial stages but to
understand other aspects of transport Caco-2 or MDCK would be required
when
one is in the LO/CD stage.
With kind regards
Shubhada
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