Bioequivalence and Bioavailability Forum • 0 hr Pre-dose concentration but less than 5% of Cmax

0 hr Pre-dose concentration but less than 5% of Cmax [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2012-03-29 21:50 (4808 d 13:01 ago) – Posting: # 8350
Views: 11,017

Dear John!

❝ What if a subject has a pre-dose concentration in period 1? Should the subject still be kept or needs to be removed since he shouldn't have any pre-dose concentration in period 1.

❝

❝ Clinic shows no deviations and data was reviewed.

Shit happens. But:

The guidance does not distinguish between period 1 and the others. Though you are right that pre-dose values in period 1 are less likely (carry-over due to too short wash-out are possible in higher ones).
If you have an SOP for pharmacokinetic repeats in place perform a reanalysis. Maybe the value will not be confirmed.
Remember the requirements for testing interferences in method validation: none out of six independent sources of matrix. If 0/6 is OK does that imply that 1/7 is OK as well? In other words even if your method was validated – in a large study you may see interferences. Keep the subject.

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Helmut Schütz

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Complete thread:

0 hr Pre-dose concentration but less than 5% of Cmax jag009 2012-03-29 19:34 [Regulatives / Guidelines]
- 0 hr Pre-dose concentration but less than 5% of CmaxHelmut 2012-03-29 19:50
  - 0 hr Pre-dose concentration but less than 5% of Cmax jag009 2012-03-29 20:10
    - Reanalysis if possible Helmut 2012-03-29 23:17
      - Reanalysis if possible jag009 2012-03-30 15:06
        
        >6 sources of matrix Helmut 2012-03-30 15:16
        
        >6 sources of matrix jag009 2012-03-30 20:40
        
        >6 sources of matrix Helmut 2012-03-31 00:23
        
        >6 sources of matrix jag009 2012-04-04 16:32
        
        Flashback Helmut 2012-04-05 16:10
        
        Flashback jag009 2012-04-05 17:51
        
        No correction if ≤5% Cmax Helmut 2012-04-05 18:08
        
        No correction if ≤5% Cmax navoday 2012-08-15 20:37
        
        excluded period(s) Helmut 2012-08-16 16:36
        
        excluded period(s) rajasekharkakarla 2019-09-20 07:57