AUCt not covering at least 80% of AUCinf [Regulatives / Guidelines]

posted by Astea – Russia, 2020-06-05 21:05 (1806 d 02:01 ago) – Posting: # 21501
Views: 19,247

Dear Friends!
I've got I question concerned to this issue.
Until now I thought that the rule of 80% AUCinf was invented in order to demonstrate that the total duration of sampling is sufficient. But consider a following case:
IR drug with T1/2=12-18 hours (according to literature data).
The last sampling time in the protocol was choosen to be 48 hours with a large step before, like: ..8 hours, 12 hours, 24 hours and 48 hours.
For several subjects the PK curves were like this:

[image]
The concentration in the last point was below LLOQ, however AUClast didn't cover 80% of AUCinf.
So I may conclude, although the rule was not followed, the duration of the sampling time was sufficient. In this case the rule may indicate: too large distance between sample time points (48-24=24) that is an error in study planning or too large LLOQ. Am I right in this conclusion? How can regulators interpret this issue?

"Being in minority, even a minority of one, did not make you mad"

Complete thread:

UA Flag
Activity
 Admin contact
23,424 posts in 4,927 threads, 1,671 registered users;
91 visitors (0 registered, 91 guests [including 13 identified bots]).
Forum time: 23:07 CEST (Europe/Vienna)

A statistical analysis, properly conducted, is a delicate dissection of
uncertainties, a surgery of suppositions.    Micheal J. Moroney

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5