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I have a technical problem when trying to use WinNonlin for calculation of Cmax
and AUCinf for a multiple dose clinical study.
The out put of the program is referring to the first AUC and to the
and I wish to have the PK values of the fourth curve. Does anyone can help me
with that. I am using two models: noncomparmental analysis and model #11
(Professional Winnonlin) for a two compartmental analysis. The drug is being
given for few weeks , 4 times a day (0, 240min,480min and 720min). At
predose time I have already a significant level of drug in the blood. What is
actually the best interval that I have to take for AUC and Cmax
if I have 3 different dose groups? Can I use the steady state
parameters or the
mean Cmax and mean AUC values?
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Liat - In WinNonlin noncompartmental analyses it is possible to
specify that you
are at steady-state. You then enter the time that the last dose was
the profile of interest.
If you are not really at steady-state, you will still get the Cmax
and AUC values.
You just need to exercise caution in how they are interpreted. For
them as 'Day 4' parameters as opposed to steady-state values.
If you are modeling the results, you can of course compute parameters from any
profile (or best of all....all profiles) and making the assumption of
stationarity, predict the steady-state profile.
With regard to the best time to assess linearity:
Steady-state is the best time to assess linearity from the point of
generalizability. That is, your results will be most defensible if they are
characterized at steady-state. However, depending on study design
(how rich your
data is) you may actually have better resolution to see subtle PK
a single dose. The the question then becomes whether the subtle
important (usually not).
Another problem I have seen is the following. Lower dose groups are at
steady-state, but in the presence of a nonlinearity, the high dose
groups have not
yet achieved steady-state. One therefore underestimates the degree of
nonlinearity. In this case it is essential to look for those 'subtle
in the data rich single dose profile.
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