Calculation of AUC0-72 [NCA / SHAM]

posted by Helmut Homepage – Vienna, Austria, 2009-01-26 16:24  – Posting: # 3123
Views: 19,545

Dear D. Labes,

sorry for the late response – I was driven by discussions about the drafted European BE-Guideline. :-D

» I would like to discuss this a bit further.
» How do you act in a truncated setting if the last sample is missing? Or if some subject has conc. <LOQ due to faster kinetics?
»
» Omit this subject from the analysis?

I have heard of CROs omitting subjects if AUC72 was stated as the primary parameter and the sample at 72 h (or earlier) was ≤LOQ. In the strict sense I would consider this correct.
But: with the current trend of moving from seening BE as a surrogate of clinical safety/efficacy to a measure of pharmaceutical performance in vivo I would go with Kamal Midha’s Mantra and accept AUCs where the absorption is completed (Clast ≥2–4 times tmax). See Example 2 in this thread. If we truncate AUCs of subjects with Clast<72 (for any treatment) at the last time point where C>LOQ (for all treatments), it should be possible to get an unbiased estimate of the T/R-ratio.* Unfortunately this method is not available in commercial software (at least not in the current versions of WinNonlin, Kinetica, EquivTest/PK).

I wouldn’t start trying to get an estimate of C72.


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