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Some time ago Michael described a phenomenon quite often seen in his Pk
studies (see below). Does anyone of you know anything citable (a
published paper or any other source like a meeting report, contribution
etc.) describing the same or similar observation? I need this for my
I found a two compartment model for my compound best describing p.o.
data and a three compartment model for the same compound best
describing i.v. data.
Thank you very much for your help.
[The rate parameters need to be sufficiently different to see 'more'
compartments. If the absorption rate constant is close (less than a
factor of 5) to any of the disposition parameter (alpha, beta, gamma, z
etc) then the oral (extravascular) route will only 'support' fewer
compartments. A (poor) example can be seen at
http://www.boomer.org/c/p4/c19/c1907.html. Simultaneous fitting of iv
and oral data can help resolve this situation - db]
PS: this is taken from the PharmPk discussion:
I have one naive question with respect to disposition of compound 'X' in
We have done Oral and IV studies for this particular compound at a
dose where it has linear pharmacokientics. In case of oral we are
compartment behaviour(mono exponential deacay), where as in case of IV
are seeing two compartment behaviour (bi exponential decay), as any one
the group has seen this kind of behaviour where similar compound
different manner with respect to disposition in the same species at a
dose. If yes what may be the possible reasons?
Thanks and Kind Regards,
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* On 29 Jul 2004 at 16:41:58, Michael.Gassen.at.4sc.com sent the
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.
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As I remember from my Ph.D. studies, the issue of Route dependent
disposiotion was discussed by John Wagner in his article
"Linear pharmacokinetic models and vanishing exponential terms:
implications in pharmacokinetics". Wagner J G Journal of
pharmacokinetics and biopharmaceutics (1976 Oct), 4(5), 395-425.
Dr. Mutasim Al-Ghazawi,
Head of Biopharmaceutics and Clinical Pharmacy Dept.
Faculty of Pharmacy-University of Jordan
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