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I am fresher with graduation. I have doubts in sas how to calculate
Cmax, Auct,Aucinf, Tmax,Rsequare, Rseq-adjust,Correlation, Lambada_Z,
Lambada_Z_lower, Lambada_Z_Higher using SAS.
Please give me suggestions for how to write SAS Pogramming for BA-BE
Plasma concentration data for all these parameters.
Thanking you,
with regards,
aditya.
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Dear Aditya,
The following link may helps you in this:
http://www.lexjansen.com/pharmasug/2005/statisticspharmacokinetics/sp07.pdf
This paper explains about the Noncompartmental analysis.
Note: As you are a fresher you have to learn the knowledge how to
calculate these by manually. They you can go ahead in this field.
Thank you,
Regards,
M.V.G.S.Raghavendra
Biostatistician
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The following message was posted to: PharmPK
Dear Aditya,
For BA studies PK parameters are usually estimated using
Non-Compartmental Analysis (NCA).
Calculating Cmax is simple: for instance by use PROC MEANS or
equivalent,
but PROC SQL can also be very useful:
PROC SQL;
SELECT subject
, period
, time AS tmax
, conc AS Cmax
FROM ctdata
GROUP BY subject, period
HAVING conc=MAX(conc)
;
QUIT;
(tmax is the time corresponding to Cmax, but be aware of multiple
occurances of Cmax.)
AUC can be calculated by using the linear or log-linear trapezoidal
rule.
This requires DATA step programming.
Good starting points for this can found in:
http://www2.sas.com/proceedings/sugi27/p229-27.pdf
or
http://www.lexjansen.com/pharmasug/2005/statisticspharmacokinetics/sp07.
Lambda_z_lower and Lambda_z_higher should either be chosen
1) by hand after inspection of a semi-logarithmic plot of the
Concentration-time data
(you can use PROC GPLOT for this), or
2) algorithmically (e.g. using an algorithm that maximizes Rsquare).
Lambda_z can be calculated using PROC REG after log-transformation of
the concentration data
in the range [Lambda_z_lower, Lambda_z_higher].
This PROC will then also provide you with Rsquare, Rsquare adjusted etc.
AUCinf is then calculated by extrapolation using:
AUCinf=AUClast + Clast/Lambda_z
where Clast is either the observed concentration at t_last or the
estimated concentration
for t_last, using the regression equation provided by PROC REG while
estimating Lambda_z.
(t_last is time-point of the last quantifiable concentration).
Kind regards,
Jan
Jan Hartstra | Sr. Biostatistician | Early Development Services | PRA
International
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The following message was posted to: PharmPK
Aditya,
In my opinion, noncompartmental analysis is a crude way to calculate
BA, but
can be useful. A particular caution is due to sampling times and
calculation
of AUC. People often use a simple trapezoidal rule to integrate AUC on
either an absolute or log scale, and then take the highest observed
concentration as Cmax and the time of that observation as Tmax. But how
likely is it that a sample was taken exactly at the time Cmax occurred?
I prefer to fit a good pharmacokinetic model (using GastroPlus(tm), but
other tools are available), which can (and usually will) provide Cmax
and
Tmax between observations. Cmax can be significantly higher than the
highest
observation in some cases. Of course, you need to be careful about a
model
that fits the data points well but is not realistic for various reasons.
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
Phone: (661) 723-7723
FAX: (661) 723-5524
E-mail: walt.aaa.simulations-plus.com
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