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The following message was posted to: PharmPK
Dear All:
We are performing some animal studies to figure out the food effects on
oral bioavailability of our compounds. We are interested to know the GI
transition time in mice, rats, cyno monkey and human. Can anyone provide
the reference? Thanks for the help.
Yilong Zhang, Ph.D.
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You may find limited information in the following:
Brian Daives and Tim Morris, Physiological Parameters in Laboratory Animal
and Humans, Pharmaceutical Research, Vol 10 (7), 1093-1095, 1993
Clemens E.T. and Stevens C.E., A comparison of gastrointestinal transit
time in ten species of mammal. Journal of Agricultural Sciences, 94,
735-737, 1980. (note: I found this reference in the RIVM report as shown
below but could not locate the journal in the Medline.
L.L. de Zwart et al., Anatomical and physiological differences between
various species used in studies on the pharmacokinetics and toxicology of
xenobiotics. A review of literature. RIVM report 623860 010, Oct 1999.)
I hope this helps.
Joseph Kim, Ph.D., RPh.
Clinical Pharmacokineticist
Antiviral CPK/Modelling & Simulation
CPDM, R&D
GlaxoSmithKline
Research Triangle Park
North Carolina 27709
U.S.A.
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The following message was posted to: PharmPK
You can find the report of de Zwart et al. at the website of our
institute:
http://www.rivm.nl/bibliotheek/rapporten/623860010.html (the report is
in
english, just download pdf)
At the moment we are actually working on an update of this report and
putting the data in a database. This database will hopefully be
available
via a website by the end of this year.
I would be grateful if anyone could send additional references on
fysiological parameter values in mice, rats, rabbits, dogs, pigs or
humans.
We focus on the GI tract, liver and kidney, but relevant data voor
inhalatory and dermal exposure will also be taken into account.
Last year we published also a review on physiological parameter values
in
children and adults [De Zwart et al. Role of biokinetics in risk
assessment
of drugs and chemicals in children. Regulatory Toxicology and
Pharmacology
2004; 39: 282-309; and
www.rivm.nl/bibliotheek/rapporten/623860011.html].
We now are planning to make such an overview also for young animals
(mice,
rats, rabbits, dogs and pigs).
Additional information for this overview is also very welcome!
Kind regards,
Adrienne Sips
AJAM Sips, PhD head department Method and Model development
National Institute of Public Health & the Environment (RIVM)
Center for Substances and Integrated Risk Assessment, U339
P.O. Box 1
3720 Bilthoven
The Netherlands
tel. + 31 30 274 2043
fax. + 31 30 274 4475
e-mail: adrienne.sips.at.rivm.nl
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The following message was posted to: PharmPK
Hello again Forum,
For human, and I imagine animal studies, the most sensitive and accurate
method of assessing GI tract transit times is Segmental Colonic
Scintigraphy
because it offers a quantitative measure of whole gut and each segment
separately. Using Indium-111 we have found that it is surprisingly slow
and
there is considerable inter-subject variation. In a recent study where
group
sizes were 12 or 13 one typical group produced whole body counts
remaining
at 74 hours of 28.7% +/-8.9 SD on placebo and and no less than 51.5%
+/-32.1
SD after codeine. That means we probably need to continue counting out
to 6
or 7 days, especially if constipatory drugs like codeine have been
given to
the volunteers.
We had not expected this slow time due to reports of 50% retention of
isotope at 24 hrs and less than 20% after 48 hours (Ref 1) but the wide
variation is well known. Diet obviously affects variation, with lipids
accelerating small bowel transit but slowing colonic transit in one
report
(ref 2) while proteins did the opposite in another reference (ref 3)
and the
fibre content of salads and fruit is known to accelerate both.
I presume that in animal work you can control the diet so accurately
that
you obtain rather more consistent results. I also presume that animal
models
predict the outcome in humans but would be interested to hear if anyone
has
evidence to the contrary.
I hope this helps answer the original question.
Andrew Sutton,
References:
1. Read NW et al. Simultaneous measurement of gastric emptying, small
bowel
residence and colonic filling of a solid meal by use of the gamma
camera.
Gut, 1986, Mar; 27(3):300-8
2. Graff et al. 2001. Standards for for non-invasive methods for
gastrointestinal motility: scintigraphy. A position statement from the
Gruppo Italiano di Studio Motilita Apparato Digerente (GISMAD)
Dig Liver Dis 2000 Jun-Jul;32(5): 447-52
3. Hammer J, Hammer K & Kletter K. Lipids infused into the jejunum
accelerate small intestinal transit but delay ileo-colonic transit of
solids
and liquids. Gut 1998 Jul; 43(10):111-6
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