Bioequivalence and Bioavailability Forum

Dear Helmut,

Thanks for your prompt reply and explanation with example! I always get prompt solution from forum to all my problems, I really appreciate it.

❝ Guidelines require the actual time, not the scheduled one.

I know it has been mentioned in the EMA guideline but could not locate in any of the FDA guideline.

❝ Why not calculate AUC₇₂ for both? In Phoenix/WinNonlin request a partial AUC (start=0, end=72).

Is the use of partial area, the best solution for the truncated study? If yes, what about the non truncated study having primary PK parameters as Cmax and AUCt, where samples up to 36 hrs were collected, but in 20 % of the subjects last measurable concentration appeared at 18 hrs (in fact in couple of subject it was only 8 hrs) and majority of the subjects got measurable concentration at 24 hrs and again few subjects got concentration at 36 hrs post dose. This situation I have encountered in one of the pMDI study and somewhat similar type of variation in the AUC was observed in the DPI and Nasal Spray studies.

❝ If you don’t have suitable software, the interpolation formula

I do have Phoenix/WinNonlin.

❝ If you don’t feel comfortable with an estimated AUC₇₂ (i.e., prefer mixed fruits), decrease the time allowance window. As an example EMA requires for studies in steady-state (τ 24 hours) a maximum deviation of 10 minutes.

I can very well implement your suggestion of the partial area, provided it is the best approach for truncated study.

Best Regards,

Ratnakar