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Does anyone have data on gastrointestinal transit times in human and
cynomolgus monkeys in the fasted and non-fasted state? The following
parameters would be appreciated:
* Average transit time throughout the GI (fed and fasted)
* Transit time
in the stomach, jejunum, duodeneum, ileum, colon (fed and fasted)
* pH of the stomach, jejunum, duodeneum, ileum, colon (fed and fasted)
Boomer site (http://www.boomer.org/c/p1/Ch11/Ch1103.html) was very
helpful, but I would like some monkey and fasted/fed comparative data.
Thanks,
Josef Strasser
SkyePharma
Associate Director of Toxicology
10450 Science Center Dr.
San Diego, CA 92121
josef_strasser.aaa.skyepharma.com
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[Two more replies - db]
From: "David Caron"
Date: Tue, 5 Mar 2002 09:40:37 +0200
To: david.-a-.boomer.org
Subject: RE: PharmPK Comparative GI transit time
The following message was posted to: PharmPK
Dear Josef,
You may try the following review article:
Dissolution Testing as a Prognostic Tool for Oral Drug Absorption:
Immediate Release Dosage Forms, Pharm. Res., Vol 15, No 1, 1998.
Best Regards,
Dr. David Caron
IPR-Israel Pharmaceutical Resources
davidc.-a-.iprx.co.il
---
From: Hans-Markus.Bender.-at-.merck.de
Date: Tue, 5 Mar 2002 08:56:26 +0100
To: david.aaa.boomer.org
Subject: Antwort: PharmPK Comparative GI transit time
The following message was posted to: PharmPK
Dear Mr. Strasser,
I can recommend a review articel (Comparison of the gastrointestinal
anatomy, ..) by TUGRUL T. KARARLI in Biopharm & Drug Disposition, 16,
page 351-380 (1995) that will answer some of your questions.
Best regards
H M Bender
Dr. Hans Markus Bender
Merck KGaA
Institut fŸr Pharmakokinetik und Metabolismus Am Feld 32
D-85567 Grafing
[Germany]
e-mail: hansmarkus.bender.at.merck.de
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The following message was posted to: PharmPK Dear Dr Strasser,
The problem with transit times all along the gut in man is the wide
variation, affected by the method, the test meal, gender and probably
the background diet of the subject, not to mention the effects of common
drugs like codeine. One possible source of good data is placebo groups
in some recent clinical pharmacology papers. An example would be the use
of methylnaltrexone to reverse opiate effects (Yuan CS et al, 1999,
Pain: 631-635). Reports on GLP-1 also contain normal data (Willms B et
al, 1996, J Clin Endocrinology & metabolism 81, 327-332).
There is also a very large literature going back a three decades to the
time when Hinton et al invented the radio-opaque pellet method at The
London Hospital. (Hinton JM, Lennard-Jones JE and Young AC 1969, Gut
10:842-847). It was refined by Sidney Phillip's group in Rochester,
Minnesota, and from a study in 73 subjects they produced a seminal paper
on the effects of gender and fibre in the diet on segmental transit
times within the different portions of the colon (Metcalf AM et al,
Gastroenterology 1987, 92, 40-47). Total colon times, ie: the time taken
from ingestion to the appearance of 50% of the pellets in faeces were :
Males: 33.3hours (SD 4.3, n= 10), females: 46.9(3.7, n=14). We have
found slightly wider variation, probably due to combining males and
females and our smaller n of 8, since our 2 placebo groups produced mean
total bowel transit times of 32.8 (SD: 3.8) and 45.9 (SD: 17.4) hours
(Sutton JA, Kilminster SG and Mould GP, Eur J Clin Pharmacol, 1997, 52:
365-369.) An interesting reference on the more modern (and less messy!)
scintigraphic technique would be the Mayo Clinic Manual of Nuclear
Medicine 1996 (ISBN 0-443-07765-7) page 314 where the average data are
listed, although they are only expressed in terms of geometric mean
amounts of radioactivity dose remaining in colon at 4 and 24 hours (ie:
0.8-1.4 and 1.7-4.0 respectively). That technique might be the most
practical for studying primates. Oro-caecal transit times are equally
well represented in the literature, as I think you would find using a
search on 'Breath hydrogen' method. It gives the time taken for the
leading edge of a lactulose test meal to reach the caecum, where
anaerobic bacteria produce hydrogen. Being very insoluble hydrogen
rapidly equilibrates with plasma in the caecum wall and is rapidly blown
off into expired air the lungs. Typical mean times are 2 hours with
coefficients of variation around 40-50%.
Gastric emptying times are highly dependent on meal type and posture and
possibly method. For example, Choi MG et al, compared scintigraphy with
the [C13]Octanoic acid breath test (Gastroenterology 1997, Apr;
112(4):1155-62) and found poor correlations. By contrast Feinle C et al
found that an MRI method compared well with scintigraphy (Gut 1999, 44,
106-111). Much of the literature illustrates how wide variation poses a
real problem for diagnosis in patients with deranged function. For that
reason we are trying to develop the use of water as a simple probe meal
with reasonably consistent times short enough to be convenient in the
clinic and to show up delayed emptying. An example was our Eur J Clin
Pharmacol paper cited above where placebo gastric t50%'s were 10.5 mins
(SD 3.6, n = 8) or 11.9 mins (SD 6.3, n = 8). This approach has also
detected delayed emptying due to posture, diabetes, stress during
migraine attacks and after morphine which incidentally correlates well
with nausea in Phase 1 studies (Murphy DB et al, Anesthesiology 1997,
87, 765-70).
I hope these references will give you useful leads by scanning their own
reference lists.
Good luck.
Andrew Sutton.
Guildford Clinical Pharmacology asutton.-at-.gcpl.co.uk
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