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Hello,
When I am studying the behavior of a new compound in healthy
volunteers and I want to calculate their pharmacokinetic parameters.
Is it preferable to calculate the average life, using all the dots or
narrow the phase terminal to achieve a good are although well dismiss
many points
Thanks a lot
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If the late points are acceptable bioanalytically, why reject them?
If on
the other hand they are at or below the method's LLOQ (estimated by
CV, Bias
or other means) you are incurring risk of error.
Ed F. O'Connor,PhD
email: efoconnor.at.cox.net
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The following message was posted to: PharmPK
I assume from your phrasing that you are looking at Non Compartmental
analysis of this new compound; in which case I would assess the apparent
rate of elimination using all points from Clast and work backwards until
you see a notable inflection of the curve (remember you should have the
data plotted semi-logarithmically), or you feel the goodness of fit has
deteriorated (e.g. adj. R-sqd. below .85). I would be extremely
reluctant to exclude any point within this interval with out a good
rationale to justify to a reviewer, I would also attempt to compare
profiles across a group and assess Lz [Lz == lambda Z == terminal/
slowest rate constant - db] over at least 3 half-lives. I'm
sure many other contributors can share similar 'rules of thumb', I think
David has some on this site.
Any 'averaging' I would do on the final parameters after NCA so you
can assess in some manner variability and range observed in your dose
group, you may also want to consider compartmental modelling if it is a
novel compound as this may help you describe it's anticipated PK better.
Probably you need to think what questions you are trying to answer with
your analysis before commencing your analysis.
Best regards,
Simon.
--
Simon Davis
Senior Scientific Consultant
http://www.linkedin.com/in/simondavis
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