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Hello all,
I have one naive question with respect to disposition of compound 'X' in
mice species.
We have done Oral and IV studies for this particular compound at a
similar
dose where it has linear pharmacokientics. In case of oral we are
seeing one
compartment behaviour(mono exponential deacay), where as in case of IV
we
are seeing two compartment behaviour (bi exponential decay), as any one
in
the group has seen this kind of behaviour where similar compound
behaves in
different manner with respect to disposition in the same species at a
same
dose. If yes what may be the possible reasons?
Thanks and Kind Regards,
Suresh.B.L
Dear Lakshminarayan,Back to the Top
Actually, we see the phaenomenon that you describe quite often in our
own work. After an oral dose, the early phase of the disposition curve
may not become apparent if absorption is the rate limiting process.
Thus you see "monoexponential" behavior after po dosing, while the drug
is actually eliminated in a biphasic manner after an iv dose.
Michael
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Hello Suresh
The situation you are referring to is commonly seen in many drugs. Upon
oral
administration,we often fail to observe the distributive phase as
distribution might occur much faster than absorption. It also depends
on
the sampling time points in the initial phase.
Were the sampling pattern similar for both iv and oral studies?
Hope this helps
Thanks
Mathangi.
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Dear Suresh
If a compound absorbed slowly, the rapidly
equlibrating and shallow compartment most likely would
not be present. This has been observed before.
Rostam
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Dear Lakshminarayan,
Your observation is very good though not very common. I have observed
such
behavior when absorption is the rate limiting factor.
hope this helps,
Jagannath
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Dear Suresh,
As stated earlier by others, this phenomenon is not uncommon, and
perhaps
more common than the true monoexponential decay after intravenous
administration, or the apparent biphasic elimination after oral
administration.
In addition to the comments by others, I would like to point to the fact
that an 'apparent' absorption rate constant (Ka) obtained from the oral
profile alone does not reflect the 'true' absorption rate constant (if
this
really exists, but that is a different topic dealt with recently). In
practice, such values are often reported, but in fact they are
meaningless.
The 'true' absorption rate constant can be obtained only by considering
the
oral and intravenous profiles simultaneously, either by simultaneous
curve-fitting or by a deconvolution procedure.
Best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Email: j.h.proost.-at-.farm.rug.nl
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)