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I want to know how to calculate AUC, Cmax and Tmax using SAS. Can I
get your ideas regarding that please?
Thanks
[A spreadsheet might be easier - db]
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Dear kabita Joshi,
Please see the following link having a program to calculate the PK
Parameters.
http://www.lexjansen.com/pharmasug/2005/statisticspharmacokinetics/sp07.pdf
(For all parameters)
http://www2.sas.com/proceedings/sugi27/p229-27.pdf
(For AUC)
--
Regards,
M.V.G.S.Raghavendra
Biostatistician
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You may want to see the book as below:
Pharmaceutical Statistics Using SAS: A Practical Guide
Author: Alex Dmitrienko, Christy Chuang-Stein, Ralph B. D'Agostino
Feng
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The following message was posted to: PharmPK
Dear Joshi,
I think you could refer to SAS programs given in below URL.
http://www.lexjansen.com/pharmasug/2005/statisticspharmacokinetics/sp07.pdf
Best regards,
Mitsuo Higashimori
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Dear Kabita Joshi,
Please be aware that there are some bugs in the code of Matos-Pita et
al. The 90%confidence interval of the point estimate is calculated
with a fixed t-value (1.761). This might result in an incorrect BE
decision. As mentioned on BEBAC the sequence effect should be
calculated with the error term "subject(sequ)". AUC-calculation is
often done using only the linear trapezoidal rule (no log-
transformation).
We compared the results of the code to WinNonlin (after fixing the
bugs) and found only minor differences for Cmax and AUCt . But one
should be aware that elinmination rate const.-calculation is done
differently in WinNonlin and the SAS code, as to why the differences
in AUC0-inf were greater.
Following code for "ANOVA" uses the correct t-value:
%macro anova(param =);
data PkNCA;
set ???.???;
if period = 1 and treatment = 1 then seq = 1;
if period = 2 and treatment = 2 then seq = 1;
if period = 1 and treatment = 2 then seq = 2;
if period = 2 and treatment = 1 then seq = 2;
ln¶m = log (¶m);
run;
ods output LSMeandiffCL = LSMeans;
ODS exclude ExpectedMeanSquares ModelANOVA FitStatistics LSMeanCL
LSMeanDiffCL;
title h = 2 j = c "Bioequivalence analysis of ¶m";
proc glm data = PkNCA;
class subject period seq treatment;
model ln¶m = seq subject (seq) period treatment/ SS3;
random subject(seq) /test;
lsmeans treatment / pdiff cl alpha = 0.1;
run;
ods output close;
quit;
data lsmeans;
set lsmeans;
format result $ 28.;
ratio=Exp(difference)*100;
upper=exp(upperCL)*100;
lower=exp(lowerCL)*100;
parameter = ¶m;
interval = trim(left('['))||trim(left(put(lower,8.3)))||trim(left
(','))
||trim(left(put(upper,8.3)))||trim(left(']'));
if 80 <= lower <= 125 and 80 <= upper <= 125 then
result = "Bioequivalent for ¶m";
else result = "Not bioequivalent for ¶m";
label interval = 'IC90%' ratio = 'Point Estimate'
result = 'Conclusion';
run;
proc print noobs l;
var ratio interval result;
run;
%mend anova;
best regards
Franz Innerbichler
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The following message was posted to: PharmPK
Dear All,
Request you to pl. suggest some descriptive literature / link
explaining Biphasic Elimination.
Does the drugs having biphasic elimination show higher variability
(inter-subject or intra-subject) during single dose clinical studies ?
Thanks & Kind Regards,
Neha Bhandari
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The following message was posted to: PharmPK
Dear All,
Request you to pl. suggest some descriptive literature / link
explaining Biphasic Elimination.
Does the drugs having biphasic elimination show higher variability
(inter-subject or intra-subject) during single dose clinical studies ?
Thanks & Kind Regards,
Neha Bhandari
[Biphasic elimination == two compartment pharmacokinetics?? See
http://www.boomer.org/c/p4/c19/c1901.html
- db]
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Dear Neha,
The biphasic elimination refers to the excretion of the drug with
simulteneous distribution of drug in the tissues. This will vary from
person to person menas, inter and intra subject variation will always
be observed.
In his case it is very much difficult to get inference from single
dose data. But with the help of single dose data you can simulate
multiple dose data and can see what is happening at steady state
concentration.
This may probably will help you.
With Regards,
Dr. Tushar Nahata
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The following message was posted to: PharmPK
Dear Tushar,
Thanks for yor response.
Just to elaborate further on my query:
I am working on a BCS Class IV compound, which has high first pass
metabolism as well.
Literature suggests that it shows a biphasic elimination pattern with
initial half life of about 6 hrs and terminal half life of about 30
hrs. This may be due to its extensive distribution (Vd > 1000 L).
This compound also exhibits high variability (%CV = 50 - 100% in
studies even with n0 subjects) in both Cmax as well as AUC values.
As far as Biphasic elimination is concerned, it will give variability
in AUC values. What could be probable reasons for variability in Cmax
values ?
Thanks & Regards,
Neha Bhandari
Research Scientist
Jubilant Organosys Ltd.
Noida, India.
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The following message was posted to: PharmPK
Dear Neha,
For a compound as complex as this, you really need something like
GastroPlus(tm) to do a proper analysis. You have so many interactions
among
solubility/dissolution, absorption, probable nonlinear metabolism, and
the
high volume of distribution that simple methods can fool you. You can
often
make a pretty picture with simple methods (i.e., the simulation line
runs
through the data points) in many different ways, but how would you know
which one is correct?
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
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Dear Neha,
Do you have any literature regarding this drug regarding its
metabolizing pattern (fast and slow metabolization) whcih can give
some insights for the biphasic elimination and the same way this may
tell about the variation in cMax also.
With Regards,
Dr. Tushar Nahata
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