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Good morning,
I would like to ask you if someone could help to me.
I am studying a new compound which have a special behaviour in plasma.
When I represent the time-concentrations I can see two peaks. The
problem is that, apparently, my compound is not stable in bile, so I
dont think this may cause by enterohepatic cycle. What could be the
reason, maybe a double absorption?
Thank you in advance
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Hi
Did you check the type of drug product?
if it is sustained release or double coated tablet (modified release
drug product), it could be possible.
Minson
--
Min Son Baek, Ph.D.
PostDoc Pharmacokinetic Team
ISIS pharmaceuticals
1896 Rutherford Road Carlsbad CA 92008
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Probably this paper can help you:
Metsugi Y. Appearance of double peaks in plasma Concentration-time
profile after oral administration depends on gastric emptying profile
and weight function. 2007 Pharm Res
The time when the second peak is observed could give you some clues.
Short time (dual absortion), long time (recirculation process).
Information from i.v. data would be useful as well.
Good luck.
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Please, see the recent study:
M. Tvrdonova, L. Dedik, C. Mircioiu, D. Miklovicova, M. Durisova
Physiologically Motivated Time-Delay Model to Account for Mechanisms
Underlying Enterohepatic Circulation of Piroxicam in Human Beings.
Basic & Clinical Pharmacology & Toxicology
Volume 104, Issue 1, 2009, Pages: 35-42.
With best regards,
Maria Durisova
www.uef.sav.sk/durisova.htm
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Double peak phenomena have been reported for many drugs, such as
pafenolol,
penicilamine, cimetidine, ranitidine, veralipride, actisomide, refocoxib
etc. There are a number of mechanisms suggested in the literature to
explain these multiple peak phenomena (e.g, two sites of absorption,
extensive biliary excretion, GI metabolism of biliary excreted
conjugated
metabolites to the parent drug or a nonconjugated metabolite which can
be
converted to the parent drug). If a drug is extensively excreted in bile
and absorbed again, usually the second peak appears right after a
meal. If
the double peak phenomena is due to the two absorption then usually the
first peak is smaller than the second peak. For rofecoxib, there are
multiple peaks observed following oral administration and exact
mechanism
is unknown although extensive mechanism studies were conducted before
the
drug was withdrawn for the market.
Chyung S. Cook, Ph. D.
Senior Director, Research
PK and Bioanalytical Sciences/Technology Resources
Baxter Healthcare Corporation
Mail Stop WG2-2S
25212 W. Illinois Route 120
Round Lake, IL 60073
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The following message was posted to: PharmPK
One of the more common factors that is routinely ignored in PK
analysis is
the effect of meals on hepatic blood flow rate, which can have an
effect on
the rate of metabolism. We don't starve subjects for 24 hours! Good data
collection will include the time at which meals were given after the
dose.
Modeling this effect is quite easy with software such as GastroPlus(tm).
Best regards,
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (NASDAQ: SLP)
42505 10th Street West
Lancaster, CA 93534-7059
U.S.A.
http://www.simulations-plus.com
E-mail: walt.at.simulations-plus.com
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First of all, I would like to thanks everybody for your answers, but
now my doubt are greater.
When I do a review of all my individual data, I can observe that there
is a great intervariability.
There is no always a doble peak in my concentration-times graphs, but
also a multiple peak is so often.
On the other hand, these others peak are usually in a (more or
less)short period of time and always, or the most, the second and
third peaks are smaller than the first one.
Somebody could explain this event?
Thank you in advance
[How big are these peaks? Could they the result of assay/sample
variability? - db]
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Or the effect of the drug itself on blood flow! vasodilators vs
vasoconstrictors
Edward F. O'Connor, PhD
78 Marbern Drive
Suffield, CT 06078
efoconnor.-at-.cox.net
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