Back to the Top
The following message was posted to: PharmPK
Dear All,
In a bioequivalence studies to calculate IC 90% to AUC, is it better
apply AUC0-t or AUC0-last ? Could somebody discuss this issue?
In a BE study of azithromycin, with mean AUC near 88%, when IC 90% was
calculated using AUC0-t, the IC90% was inside 80-125% interval, but
when AUC0-last was evaluated the IC90% was outside 80-125% interval
(79,9 - 108). Is this formulation BE or not? Is right to apply AUC0-t
or AUC0-last?
Please, give me your opinion.
Thanks
Daniel
Back to the Top
The following message was posted to: PharmPK
Dear Daniel,
would you please specify what you mean with AUC0-t?
Do you mean AUC up to the last quantfiable concentration, and then
adding a triangle to the next planned sampling point (where C is set
to zero). This is called AUCall and to my knowledge is an "invention"
of Pharsight Inc. (WinNonlin).
Please have a look at http://www.boomer.org/pkin/pk/AUCinf.jpg
I guess IC 90% is the 90% confidence interval ;-)
>In a bioequivalence studies to calculate IC 90% to AUC, is it better
>apply AUC0-t or AUC0-last ?
Ok, AUC0-last is the primary parameter in the European Union (where
AUC0-last must cover at least 80% of AUCinf).
>In a BE study of azithromycin, with mean AUC near 88%, when IC 90% was
>calculated using AUC0-t, the IC90% was inside 80-125% interval, but
>when AUC0-last was evaluated the IC90% was outside 80-125% interval
>(79,9 - 108). Is this formulation BE or not? Is right to apply AUC0-t
>or AUC0-last?
You can't "pick out the best" [(c) G. Tucker] in a BE study. Hopefully
you have stated one parameter in your protocol, and this must be the one
you rely on. Otherwise you will run into multiplicity (not to mention
credibility...) issues.
By the way, your point estimate is -12%, therefore in my experience
regulators will not willingly start a great deal of discussion with you
about which parameter "shows" BE and which one not.
best regards
Helmut
--
Helmut Schutz
BEBAC
Consultancy Services for Bioequivalence and Bioavailability Studies
Neubaugasse 36/11
A-1070 Vienna/Austria
tel/fax +43 1 2311746
http://BEBAC.at Bioequivalence/Bioavailability Forum at
http://forum.bebac.at
http://www.goldmark.org/netrants/no-word/attach.html
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)