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Dear All,
I'm planning to conduct a bioavailability study in humans. Should I use
the same
dose level for Iv and oral administration. if I assume a linear PK, can
I use
two different doses. I would appreciate if someone could provide me with
his/her opinion.
Many thanks
Samia
Dear Samia:Back to the Top
It is perfectly possible to use any dose at all, just so long
as each subject gets the drug both IV and orally, in the same dosage
regimen. There is no need for a washout period, and no need to compare
AUC's. You just give each subject or patient any dose you wish, and
make sure they are by both IV and PO routes, intermixed or sequential.
Then the fraction absorbed is simply another PK parameter in your
population PK model. No big deal. Easily computed.
You can go to our web site www.lapk.org and get other
information about population PK modeling, especially the nonparametric
models, as they are consistent, and statistically much more efficient,
than the currently available parametric methods. You get better results
than by using parametric methods. Look at new advances in pop modeling
on our web site, and also go to teaching topics.
Very best regards,
Roger Jelliffe
Roger W. Jelliffe, M.D. Professor of Medicine,
Division of Geriatric Medicine,
Laboratory of Applied Pharmacokinetics,
USC Keck School of Medicine
2250 Alcazar St, Los Angeles CA 90033, USA
Phone (323)442-1300, fax (323)442-1302, email= jelliffe.aaa.usc.edu
Our web site= http://www.lapk.org
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Hi Samia,
there is no need for you to dose at the same level per iv and po. The
most important is to get the iv as a reference and the po to get your
bioavailability calculation.
Regarding the dose level you should perform an escalating dose study if
you want to ensure your assumption about the PK linearity. This will
give you several points to calculate the bioavailability.
Hope this helps,
Frederic Doc (ex Pfizer)
CEO, ADFINIS consulting
Greetings to all.Back to the Top
Frederic Doc wrote:
> Regarding the dose level you should perform an escalating dose study
if
> you want to ensure your assumption about the PK linearity.
I agree that ascending order is de rigueur if it is a genuine NCE but I
would have thought it much better to randomise the order of the
(minimum of 3) oral doses to avoid a period bias if it is a well known
compound.
Andrew Sutton
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)