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Dear all,
Just a basic query. Plasma concentration profile of my drug after oral
administration in rabbits shows no absorption phase even if sampling
is started from 2 miniutes post dose i.e it is simmilar to a profile
obtained after i.v. administration. While modelling the above data I am
using PK i.v. bolus model (Win non lin). Is it justified.
Thanks in advance
Regards
Nitin
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Nitin Mehrotra wrote:
> Just a basic query. Plasma concentration profile of my drug after oral
> administration in rabbits shows no absorption phase even if sampling
> is started from 2 miniutes post dose i.e it is simmilar to a profile
> obtained after i.v. administration.
I find this almost beyond belief that an oral dose can be fully
absorbed within 2 minutes. How exactly do you give it orally? Are you
using a gavage tube? Perhaps it going down the trachea and being
rapidly aborbed! Has anybody else see such rapid absorption of an oral
dose?
> While modelling the above data I am
> using PK i.v. bolus model (Win non lin). Is it justified.
The justification depends on what you want to do with the model
results. If the model describes your data then its probably fine for
prediction by interpolation but obviously you cannot use it to predict
absorption.
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.at.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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I have seen this thing happening with one of our compounds BUT in MOUSE.
Rabbit it's highly unlikely as far as my experience goes. Tracheal
administration ?? Well I am not too sure. Depends upon the volume
administered.
Yati Chugh
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I have seen this thing happening with one of our compounds BUT in MOUSE.
Rabbit it's highly unlikely as far as my experience goes. Tracheal
administration ?? Well I am not too sure. Depends upon the volume
administered.
Yati Chugh
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We have observed such fast absorption phase after a
intraduodenal administration of a quinolone solution
but never after oral administration with a gavage
needle
Marival
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Nitin,
I have seen this phenomenon with one of the compound I worked with only
at the TOXIC (LD20) dose where the first sample (15 min after dose)
showed the highest plasma conc. It was however, due to the toxic dose
causing spasm of the pyloric sphincter -- absorption saturated and
became zero order for the next 8 hr and not due to complete absorption
of the administered dose. The remainder of the dose sits in the stomach
and slowly released to the small intestine from where it was absorbed.
This was unique due to the irritation of the chemical we were testing
without adjusting for pH to simulate actual human poisoning scenarios.
I agree with Nick to treat it as iv data in order to get kinetic
parameters with reasoning for its use.
Shakil A. Saghir, M.S.P.H., Ph.D.
Senior Research Toxicologist
The Dow Chemical Co.
1803 Bldg., Midland, MI 48674
Phone: (989) 636-8708, Fax: (989) 638-9863
Email: ssaghir.-at-.dow.com
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Dear Nitin,
We have observed such kind of pk behaviour of some compounds given
orally to mice where 1st time point (10 to 15min) is the tmax for
some highly soluble compounds given as CMC suspension through oval
gavage needle.
The oral profile looks exactly like an IV profile.
While modelling it depends on what you are looking for? After
modelling how will you use that data? For us it was sufficient
doing NCA using winnonlin.
Regards,
B.L.Suresh.
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Could this be an analytical problem? If sample analysis involved LC-MS,
perhaps elements of the dose vehicle are causing ion suppression at the
earlier time points leading to under-estimation of the plasma
concentration?
Adrian Jackson
Head, Analytical Sciences
CTL, Alderley Park
Cheshire
SK10 4TJ
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