Bioequivalence and Bioavailability Forum

Hi John!

❝ Can I use truncated AUC if the drug has an average half-life of 25-30 hours? The upper range can be as high as 60 hours but my 6 subjects in a pilot all have t1/2 no greater than 27 hours. If I go without truncated AUC then i will probably have to sample out to 120-144 hours. The AUCt/AUCinf ratio on average (n=6) is 90%.

FDA does not specify what a “long half-life” is. In my experience everything on the average (!) ≥24 hours is OK. The end of the respective section is a little bit strange:

For drugs that demonstrate low intrasubject variability in distribution and clearance, an AUC truncated at 72 hours (AUC_{0-72 hr}) can be used in place of AUC_0-t or AUC_0-∞. For drugs demonstrating high intrasubject variability in distribution and clearance, AUC truncation warrants caution. In such cases, we also recommend that sponsors and/or applicants consult the appropriate review staff.

(my emphases)
Canada and EMA don’t make a distinction between low/high variability. Personally I don’t get FDA’s point.

Side note: Canada does not specify in their current guidance what a “long half-life” is as well (was 24 hours in their 2005 guidance). In Europe you may use AUC₇₂ irrespective of the half-life.

PS: Pleeeze, no more multiple blanks in your posts! Or are you using a typewriter, scanning the text, sending it through OCR and pasting it in here?