Bioequivalence and Bioavailability Forum • AUCt not covering at least 80% of AUCinf

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

posted by Astea – Russia, 2020-06-05 21:05 (1414 d 00:18 ago) – Posting: # 21501
Views: 12,999

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 T_1/2=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:

AUCt not covering at least 80% of AUCinf ratnakar1811 2013-03-05 08:30 [Regulatives / Guidelines]
- AUCt not covering at least 80% of AUCinf d_labes 2013-03-05 11:12
  - AUCt not covering at least 80% of AUCinf ratnakar1811 2013-03-06 08:50
    - AUCt not covering at least 80% of AUCinf ElMaestro 2013-03-06 11:10
      - ADME-tox? Helmut 2013-03-06 14:35
        
        ADME-tox? ElMaestro 2013-03-06 16:40
        
        OT Helmut 2013-03-06 17:19
        
        OT ElMaestro 2013-03-07 17:19
        
        OT Helmut 2013-03-07 17:26
    - Science vs. regulations Helmut 2013-03-06 14:30
      - Science vs. regulations cakhatri 2013-03-10 08:59
        
        ratio = difference of logs! Helmut 2013-03-11 01:17
      - Science vs. (EMA) GL aka PK primer Helmut 2013-03-11 03:17
      - Science vs. regulations qualityassurance 2020-04-23 14:11
        
        Science vs. regulations Helmut 2020-04-23 17:32
        
        Science vs. regulations Achievwin 2020-05-07 22:59
        
        Science vs. regulations Helmut 2020-05-07 23:54
    - AUCt not covering at least 80% of AUCinf Brus 2018-11-20 13:01
      - AUCt not covering at least 80% of AUCinfAstea 2020-06-05 19:05
        
        So what? Helmut 2020-06-06 12:02
        
        Carrot and whip Astea 2020-06-06 21:11
        
        Gedankenexperiment Helmut 2020-06-07 12:41
        
        Dead dogs mittyri 2020-06-07 20:32
        
        Aber meine Herren das ist keine physik Astea 2020-06-08 00:08
        
        Aber meine Dame, das ist alles Unsinn! Helmut 2020-06-08 01:04
        Bizarre paper Helmut 2020-06-08 12:43
        
        Bizarre paper ElMaestro 2020-06-08 15:33
        
        OT: Bias of AUCt, AUCall, pAUC Helmut 2020-06-08 15:53
        
        OT: Bias of AUCt, AUCall, pAUC ElMaestro 2020-06-09 08:45
        
        OT: Bias of AUCs; example Helmut 2020-06-09 14:07
        
        Maxwell's demon Astea 2020-06-12 14:15
        
        Dead dogs Helmut 2020-06-08 10:40