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dear all,
i would like to know the general absorption pattern of any drugs
which is administered through extravascular route (po, sc,im,ip) in
rodents. ( rat and mouse)
could any one help me regarding the same.
thanks and regards
shashi
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All,
I have studied absorption properties from all sorts of extravascular
dosage froms in a plethora of species. In all cases I have taken
cumulative absorption plots and converted them to rate of absorption
plots. In every single case, I have gotton a much better evaluation
by looking at rate of absorption plots. Cumulative plots have
innumerable disadvantages, and I have discussed these in the reference
below -- a totally forgotten paper (Ah!!!) -- one which John Wagner
hated, since it disputed some of his interpretation of a set of data
(NO REPRINTS AVAILABLE):
Boxenbaum, H. Pharmacokinetic determinants in the design and
evaluation of sustainedrelease dosage forms. Pharmaceutical Res. 1:
8288 (1984). NO REPRINTS AVAILABLE
In most cases, in all species with all types of dosage forms, rate of
absorption is "triexponential-ish." You start out at zero, rise to
Cmax, decay at a relatively rapid rate, and then decay at a slower rate.
If you have an IV, rate of absorption (from Loo-Riegelman method) can
easily be calculated from the Excel program below. You need get it
from Robert (Bob) Shumaker, but you will have to find out where he is
now. He may be in Maryland at a firm specializing in topical dosage
forms (?). Maybe check the AAPS listing/directory. If you have
exhaused all possibilites of contact, you can write me, but only with
the subject title "ABSPLOTS." Contact me at clerkmaxwell.at.hotmail.com.
Shumaker, R.C., H. Boxenbaum & G.A. Thompson. ABSPLOTS: A Lotus 123
spreadsheet for calculating drug absorption rates. Pharmaceutical
Res. 5:247248 (1988).
BTW, if you can fit a bi- or tri-exponential function to data does not
mean you have first-order absorption. It only means you have an
empirical function that may be very useful. This kind of information
comes from the 1960s through the 1980s.
Best wishes, Harold.
Harold Boxenbaum, Ph.D.
Pharmacokinetic Consultant
Arishel Inc.
14621 Settlers Landing Way
North Potomac, MD 20878-4305
Email: harold.at.arishel.com
Website: www.arishel.com
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The following message was posted to: PharmPK
Harold,
As you have noted so well, Ka is not a constant!
We've seen similar patterns in the vast majority of drugs we've
simulated -
sometimes even more complex, frequently with a (usually mild) "second
peak"
in the colon.
I think it's important to ask why? When we see this type of behavior,
it's
telling us something important about the drug or the formulation. For
some
drugs, it's a permeability issue (e.g., affected by different degrees of
ionization at different pH, and/or carrier-mediated influx or efflux
transport). For others, it's solubility. For others, dissolution. For
some,
precipitation. And for some, several of the above.
As you noted, fitting curves that give pretty pictures can be wrong, but
useful - if used within the limits of the fitted equation. Very often
the
absorption rate behavior at one dose level is quite different at
another, so
the pretty picture at one dose may not provide a useful model for a very
different dose. A good mechanistic model that accounts for the actual
underlying factors causing Ka to change with time can be useful over a
wide
range of doses.
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
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The following message was posted to: PharmPK
Dear All,
We have seen these pattern in most of our oral Pharmacokinetic studies
(cetirizine, propranolol, ranitidine, rifampin, diclofenac,
glibenclamid,
gliclazide, metformin,etc.) When we report it, the referee don't like
it. In
mean data usually it disappers.
We have seen it as multiple peak phenomena that is not related to
formulation. It is also nice to know that the PD effect is also
affected in
antidiabetic drugs.
Sima Sadrai, PharmD, PhD
Associate Professor
Department of Pharmaceutics
Faculty of Pharmacy
Tehran University of Medical Sciences
Tehran
Iran
Email:sadrai.aaa.sina.tums.ac.ir
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