Bioequivalence and Bioavailability Forum • Metrics for multiple profiles

Metrics for multiple profiles [NCA / SHAM]

posted by d_labes – Berlin, Germany, 2009-12-03 09:58 (5617 d 19:12 ago) – Posting: # 4409
Views: 11,768

Dear Helmut!

❝ Only if your drug shows no diurnal variability, the first 8 h profile

❝ on day 4 is sufficient. If your drug's PK is influenced by some

❝ circadian rhythms, you have to measure a full 24 hours cycle

❝ (i.e., three profiles).

I have a question.

How would you describe these three profiles?

Each with their own PK metrics (AUC, Cmax, tmax and what ever else)?
Overall AUC, Cmax, tmax?
Both?

If we take the first or last option and it comes to the statistical evaluation we have the burden to show bioequivalence for at least 3x more parameters than usual.
Or can we restrict the bioequivalence decision to lets say profile 1?
And see the other profiles only as secondary?

I remember a study with Aescin (12 h dosing interval), we have done long ago, with a marked difference between the morning and evening profiles. Much lower concentrations in the second profile, but also much more variable in Cmax / Cmin there.
Using the metrics of each profile we were able to show equivalence for the first profile but not for the second with respect to Cmax.
PTF was beyond good and evil (CV very much higher than 30%).
Bioequivalent?

—
Regards,

Detlew

Complete thread:

Statistics in multiple dose study ratnakar1811 2009-12-01 11:09 [NCA / SHAM]
- Statistics in multiple dose study Helmut 2009-12-02 00:20
  - Statistics in multiple dose study ratnakar1811 2009-12-03 07:36
    - Statistics in multiple dose study Helmut 2009-12-03 14:53
      - Statistics in multiple dose study ratnakar1811 2009-12-04 08:21
  - Metrics for multiple profilesd_labes 2009-12-03 08:58
    - Metrics for multiple profiles Helmut 2009-12-03 15:50
      - Metrics for multiple profiles d_labes 2009-12-03 16:02
        
        Metrics for multiple profiles Helmut 2009-12-03 16:11
      - PTF is another story d_labes 2009-12-03 16:17
        
        PTF is another story Helmut 2009-12-03 16:42
        
        the flatter is better? d_labes 2009-12-04 08:46
        
        Biopharmaceutical history Helmut 2009-12-04 12:35