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Recently I came across a document that author claimed
they observed time dependent PK based on plasma
concentrations: Comparison of PK profiles at cycle 1
and 8 showed that significantly higher concentrations
were observed at cycle 1 suggesting time dependent PK.
However, the AUC and CL were not significantly
different between the two cycles so IMO there is no
time dependent PK. Any comments?
Rostam
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Dear Rostam,
I am not sure how you can have significantly higher concentrations but
similar AUC and CL values. What concentrations do they talk about? What
is meant by "significant difference? How were the PK parameters
estimated? Were there any significant changes in the volume of
distribution of the compound over this time period?
I am afraid you have to provide some more information about the time
profile of the drug concentrations.
Toufigh Gordi
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Dear Toufigh,
There were no specific info provided as at what time
points statistically significant difference was
observed (cannot recal waht test was used) in plasma
conc between the cycles. From the time conc profile it
appeared that the terminal phase was shifted (the
authors refere to as 'rebound') but apparently not
enough to affect the AUC. PK parameters were calulated
using compartmental model and no sig changes in Vd
reported. I still think these data do not support time
dependent PK.
Rostam
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)