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The following message was posted to: PharmPK
Dear Colleagues:
I have three questions:
1) Often oral CL calculated in the absence of any info
on F; I believe even WinNonlin using non-compartmental
approach does this as well. Without having IV data,
relating AUC at high oral doses to altered CL or F is
rather questionable. I would like to hear from your
opinion on this.
2) In some cases when you cannot calculate the
elimination rate constant from oral curve due to no
appreciable drop in concentration (flat terminal
phase), IV elimination rate constant is used to
estimate AUCinf for oral. In theory for most drugs,
you expect to have very similar terminal elimination
half-lives for both IV and oral routes but this may
not be true for all compounds and it may generate
inaccurate/misleading values (potentially
underestimate the AUCinf). I would like to know if
anyone used this approach in any submission to FDA or
other regulatory agencies?
3) One may say why bother with AUCinf and use AUClast
then the question is: if the last quantifiable time
point for IV and oral are not the same, is it better
to use AUC up to the point for which we have data for
both IV and oral or just use AUClast regardless of if
the last quantifiable time points are matching?
Regards
Rostam
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)