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The following message was posted to: PharmPK
According to FDA guidance, at least three consecutive trough should be
taken to determine whether the SS is reached. It will not be practical
trying to catch the Cmax without a PK profile. I would check with my
statistician to see what standard method should be used. With 3 points,
you can probably do linear regression and based on the p value of the
slope for the null hyposes that is different from zero.
Best regards,
Sam Liao, Ph.D.
PharMax Research
270 Kerry Lane,
Blue Bell, PA 19422
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The following message was posted to: PharmPK
Dear Willi Cawello,
you wrote:
>Please keep in mind Cmin is not the plasma level prior to the next
dose.
I agree.
>The plasma level prior to the next dose is Ctrough.
I disagree.
I think, that the common meaning of Cmin is correctly expressed with
"trough", i.e., "the minimum point of a complete cycle of a periodic
function" (ref. Meriam-Webster's Dictionary). The plasma level prior to
the next dose should be called "pre-dose concentration" or "Cdo"; it
equals the minimum concentration only, if there is no delay in
absorption or "Tlag".
Just consider the following simple model with a lag-time of two hours:
c=100*EXP[-0.1*(T-2)]-100*EXP[-1*(T-2)]
with tau=24 hours we obtain a pre-dose concentration of 11 units, but
the minimum concentration will be 9 units two hours later, i.e., if we
call the "pre-dose" "trough" our error will be 22%.
Anyhow, it's fine to monitor pre-dose-concentrations during saturation
up to steady state (my concern is only terminology).
Best regards,
Helmut Schuetz
Head biometrics
Biokinet GmbH
Nattergasse 4
A-1170 Vienna/Austria
email helmut.schuetz.at.chello.at
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)