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The following message was posted to: PharmPK
Hi all,
In its "Guidance for Industry. Bioavailability and Bioequivalence
Studies for Orally Administered Drug
Products - General Considerations", (2003)
(http://www.fda.gov/cder/guidance/5356fnl.pdf) FDA writes (p. 9):
"We recommend that peak exposure be assessed by measuring the peak drug
concentration (Cmax) obtained directly from the data without
interpolation."
Point. No explanation. No references.
Why interpolation is generally wrong? I believe the problem was
discussed in the past, however I failed to found relevant references.
Also, I did not succeed searching PharmPK archives.
If anyone can point me an appropriate (and not very difficult to obtain
:-) literature, or simply can give clear arguments for (against?) the
FDA's statement I shall be very grateful.
I think the similar question may be asked about the practice of
determining Tmax, though this case I know some papers which touch the
problem.
Thank you in advance.
Best regards
Wojciech Jawien
Jagiellonian University
Krakow
Poland
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For what is worth, you can see my opinion on this matter in chapter 17
of
Aldo Rescigno, Foundations of Pharmacokinetics, Kluwer/Plenum/Springer,
2003.
If that book is not available in your library I can send you a short
summary of the relevant part.
Regards,
Aldo Rescigno
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The following message was posted to: PharmPK
Wojciech,
You wrote: - - " - .(Cmax) obtained directly from the data without
interpolation." - "Why interpolation is generally wrong?"..
My understanding is interpolation requires you to assume SOME KIND OF
model. And probably regulators at that time (whenever it was written)
were not comfortable with model assumptions. It is thought that
empirical evidence is generally convincing than inter/extrapolations.
So, I don't know if the given statement means interpolation is wrong.
Remember, it is called guidance and is not a statutory requirement.
One side of this coin is:---
If you have reasonable knowledge about PK of your drug (which is true
in most cases by the time you want to do BA/BE study), you can come up
with a sampling strategy to capture Cmax reasonably well.
The flip side is:--- By this time, you also know the PK model
reasonably well. So, why not use it?
There have been a few instances where equivalent battle has been
fought (conventional versus model). It will be interesting to hear
what others have to say.
Pravin
--
Pravin Jadhav
Graduate Student
Department of Pharmaceutics
MCV/Virginia Commonwealth University
DPE1/CDER/OCPB/Food and Drug Administration
Phone: (301) 594-5652
Fax: (301) 480-3212
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)