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Dear All
Please let me know How to calculate the percentage absorption of an
drug after oral administration
Thanks in advance
Regards C.Raghavender
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Raghu
You could use Wagner Nelson (WN) or Loo Riegelman Method (LR) of
deconvolution to get percentage drug absorbed. Wagner Nelson works
well for drugs that follow a single compartment PK where as Loo
Riegelman Method is good for drugs that follow multicompartment PK and
using the latter you would require drug conc -time profile after
Intravenous administration to deconvolute the drugs c-t profile after
oral admininstration. The WN Method can be done using excel however
would be challenging to determine drug absortion for LR Method and
WinNonLin would be easier to use. These examples are very well
explained in Milo Gibaldi and Donald Perrier's Pharmacokinetics. If
you are not familiar with pharmacokinetics then you could also find an
easy explanation to drug absorption under Chapter 7 of Applied
Biopharmaceutics & Pharmacokinetics by Leon Shargel and Andrew B. C.
Yu (5th edition).
Hope this helps
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The following message was posted to: PharmPK
Dear Manish and Raghu,
The original question was regarding how to calculate the percentage
absorption after oral administration. This question can be interpreted
at
least two ways: (1) one or more doses have been given and Cp-time data
are
available, and now the percent absorbed is desired, or (2) the dose
has not
yet been given, and a prediction of percent absorbed is desired.
Manish's reply is not correct, but it's not his fault. The old
literature
used the word "absorption" with respect to Wagner-Nelson and Loo-
Riegelman
methods, these methods are not capable of calculating absorption. They
do
deconvolute systemic availability. Only in the special case where
there is a
complete absence of first pass extraction in both the gut and liver will
this be equal to absorption, but it is not generally so.
Absorption means only drug leaving the lumen and entering the
enterocytes -
nothing more. Some drugs are well-absorbed but have very low
bioavailability
(saquinavir, for example, is typically absorbed over 80% but has a
bioavailability of <1% - Wagner-Nelson and Loo-Riegelman methods would
provide the <1% value, not the 80% value).
Calculating the percent absorbed from oral Cp-time data can be done if
the
pharmacokinetic parameters for the drug are known, e.g., from IV data.
If PK
parameters are unknown, but there are sufficient data from oral doses at
more than one dose level, then a single model can often be fitted
across all
dose levels simultaneously with software like GastroPlus(tm) and both
pharmacokinetic parameters and first pass extraction can be estimated.
However, if the data are insufficient, there will be multiple
solutions and
PK parameters will only be calculable normalized to the unknown fraction
bioavailable F (e.g., CL/F, Vd/F).
Estimating percent absorption before a dose is given requires an
understanding of permeability, solubility, and dissolution for the
drug in a
particular dosage form. GastroPlus simulations can usually predict Fa
with
reasonable accuracy for drugs that are passively diffused, as long as
the
appropriate physicochemical properties and permeability are known, and a
formulation is specified. Of course, there are always drugs that exhibit
unusual behaviors which are unknown, or at least not quantifiable,
until the
dose has been administered and data have been collected. These can
include
transport across the gut epithelium (influx and/or efflux),
solubilization
effects (e.g., bile salts), degradation in the lumen, and
precipitation in
the lumen. All of these phenomena can be included in simulations - if
you
know they will occur.
Best regards,
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.aaa.simulations-plus.com
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The following message was posted to: PharmPK
Dear Raghu,
I'm not sure what you want to calculate. If your aim is to calculate
absorption ratio from gastrointestinal tract (Fa) in nonclinical
study, I recommend the portal-systemic blood concentration difference
(P-S difference) or the three-points method. You can obtain these
method from following literatures;
For the portal-systemic blood concentration difference,
1. Ueda S, Yamaoka K, Sawai Y, Nakagawa T. Introduction of
recirculatory analysis into portal and systemic concentration
difference method. Biol Pharm Bull. 2001 Nov;24(11):1298-304.
2. Moriwaki T, Yasui H, Shigemoto Y, Yoshida NH. A recirculatory model
for local absorption and disposition of ciprofloxacin by measuring
portal and systemic blood concentration difference. J Pharm Sci. 2002
Jan;91(1):196-205.
For the three-points method,
3. Ueda S, Yamaoka K, Yui J, Shigematsu A, Nakagawa T. Evaluation of
capacity-limited first-pass effect through liver by three-points
sampling in portal and hepatic veins and systemic artery. Pharm Res.
2002 Jun;19(6):852-7.
Incidentally, I note we cannot separately evaluate Fa from metabolism
in the GI tract (Fg) even if we these methods.
Best regards,
Mitsuo Higashimori
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Dear Raghu,
You can use deconvolution, wagner nelson or loo reegalman method for
computation of absorption rate constant and then you can calculate
percentage absorption.
Regards,
Tushar Nahata
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The following message was posted to: PharmPK
Dear All,
I am following this discussion. It seems very interesting. One doubt
came
in mind by reading all the comments.
Percentage absorption by oral route and percent bioavailable is the same
thing or two different things ? If they are the same then by doing IV
study
one can estimate the percentage bioavailable after oral route or one can
plan in situ drug absorption study in rat or everted sac model in rat
to
estimate the percentage absorption.
regards
Dr. Amol A. Raje
Wockhardt Research Centre
Aurangabad
India.
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The following message was posted to: PharmPK
Hi Amol,
Bioavailability is not the same as percentage absorbed from the gut.
Bioavailability is the percentage of drug that survives the first-pass
metabolism in the gut and liver. It is therefore lesser than percent
absorbed depending on the extraction ratio of the drug in the gut and
liver.
Regards,
Sheila
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One way would would be give the drug IV ,intraportallly and orally to
the same animal. You would know bioavailability , first pass effect
by the liver. From this can estimate aborption from the gut. We did
this several years ago with Accutane. Drug Meta & Disp Vol 12 (2)
page 143-147, 1984. Stanley Cotler
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