Back to the Top
The following message was posted to: PharmPK
Dear Shawn,
Your statement:
"3.Regarding the absorption, one generally does not know if the
absorption
is first or zero order, because its raw data, and it depends on the drug
structure."
implies that it must be one or the other - i.e., first or zero order.
Perhaps that was not your intention, but it's important to note that, at
least for oral doses, it is never really first or zero order, although
there
are special conditions under which such models can be useful.
Students need to learn that simplifying assumptions are just that, and
under
what conditions various simplifications are appropriate, and when they
are
not. The real mechanistic behavior of how drug molecules transit the
gastrointestinal tract, get into solution, get absorbed, survive first
pass
extraction in the gut wall and liver, and reach the systemic
circulation is
an extremely complex process.
Best regards,
Walt
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (NASDAQ: SLP)
42505 10th Street West
Lancaster, CA 93534-7059
U.S.A.
http://www.simulations-plus.com
E-mail: walt.-at-.simulations-plus.com
Back to the Top
The following message was posted to: PharmPK
Hello Walt,
Thanks for your interesting comments.
I agree, the determination of order of a process (especially PK
processes of
membrane transfer and transformation) should always be done with the
disclaimer the process is "under observation", and says not very much
(if
anything at all) about the real underlying mechanisms and/or driving
forces
involved.
Perhaps you would agree since we ordinarily derive clinical PK
parameters
from global systems in lieu of local processes (e.g., Ka from plasma not
jejunal Peff), then the myriad of complexities in oral drug
absorption, when
not distracting from the at-hand application, can be forgiven. But
you are
right; at worst, such discussions should be prefaced with "...from a
practical point of view only..." or vice versa.
Kind regards,
-Shawn
SHAWN SPENCER, PHD.
Assistant Professor of Biopharmaceutics
College of Pharmacy and Pharmaceutical Sciences
Florida A&M University
Tallahassee, FL 32307
shawn.spencer.-at-.famu.edu
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Drug input sigmoidal" as the subject | Support PharmPK by using the |
Copyright 1995-2011 David W. A. Bourne (david@boomer.org)