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The following message was posted to: PharmPK
Dear PharmPK users,
We are currently looking for a study method to investigate NCE
stability in
the intestinal fluids.
Have any of you optimized such a method ?
Which intestinal, pancreatic and/or biliary enzymes should be
considered in
that focus ? With which concentrations ?
Are there any bibliographic references that detail the GI fluid
enzymatic
contents and the interspecies differences ?
Thanks a lot for your help.
Best regards
Olivier Lacombe
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The following message was posted to: PharmPK
Dear Olivier,
We have developed an "in vitro digestion model" which simulates the
conditions in the human gastrointestinal tract. We use the model to
estimate how much of a certain compound is released from its matrix
after
ingestion, e.g. contaminants from soil, contaminants from toys,
toxins from
food.
During development we took a close look at human physiology to
prepare the
different juices (saliva, gastric juice, duodenal juice (from the
pancreas)
and bile juice). We developed a model that simulated fasted
conditions and
a model that simulates fed conditions. The composition and the rationale
behind the experimental model are published. See below. Perhaps you
can use
this approach to test the stability in intestinal fluids.
Oomen AG, Rompelberg CJM, Bruil MA, Dobbe CJG, Pereboom DPKH, Sips AJAM
(2003) Development of an in vitro digestion model for
estimation of
bioaccessibility of soil contaminants. Arch. Environ. Contam.
Toxicol. 44, 281-287.
Versantvoort CHM, Oomen AG, Van de Kamp E, Rompelberg CJM, Sips AJAM
(2005)
Applicability of an in vitro digestion model in assessing the
bioaccessibility of mycotoxins from food. Food and Chemical
Toxicology 43, 31-40.
Some additional information about human physiology can be found in a
report
by the RIVM (in English). This report can be found at our website
http//www.rivm.nl/en/
De Zwart LL, Haenen HEMG, Versantvoort CHM, Sips AJAM (2002)
Pharmacokinetics of ingested xenobiotics in children: a
comparison
with adults. Report no. 623860011, National Institute for Public
Health and the Environment, Bilthoven, The Netherlands.
Hope this helps. Best wishes,
Agnes
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Dear O. Lacombe,
You can study the Gastric and Intestinal stability of NCEs by
simulating the Gastric and Intestinal environments in the laboratory.
Briefly, you can add all the contents of Human Gastric and Intestinal
fluids and add the NCE of known concentration and allow it to stay in
that environment untill the end of Gastric Transit time,
approximately for about 3 hrs (with appropriate temp). You can check
the stability by sampling the NCE from the combined mixture
periodically.
You can refere USP for the composition of Gastric fluid and
Intestinal fluid.
As far as I know you have to consider Pepsin enzyme in studying
Gastric stability and Pancreatin enzyme in studying Intestinal
stability,
You can refer the following useful articles
E.A. Gadkariem, F, Belal et al., (2004), Stability studies on
diloxanide furoate: effect of pH, temperature m Gastric and
intestinal fluids, IL Farmaco, 59: 323 - 329.
Simon P Joel, Peter I Clark et al (1995) STability of the iv and oral
formulation of etoposide in solution, Cancer Chemotherapy and
Pharmacology 37: 117 - 124.
E.A. gadkariem, H. A, El - Obeid et al., (2003), Effects of alkali
and simulated gastric and intestinal fluids on danazol stability.
Journal of Pharmaceutical and Biomedical Analysis. 31: 743-751.
Regards,
Rajesh.O.S.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)