Difference between actual and published PK parameters [Study As­sess­ment]

posted by dshah  – India/United Kingdom, 2022-02-14 18:39 (91 d 01:05 ago) – Posting: # 22781
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Hi Loky do:

» the study practical results for t1/2 was 8.8 Hours, the AUCextra/AUCobs % values for all volunteers were below 20%, resulting in AUC0-t/AUCobs% values of more than 80%; hence, the sampling times’ intervals and concentrations were sufficient to detect extent of drug absorption. Also, the limit of detection was from 5.00 – 1000 ng/mL, as the LLOQ represented 1% of practical results of practical results of Cmax for test and reference products

I agree with Helmut.
I believe that as per regulatory guideline- we are doing NCA for BE determination over compartmental analysis, so unless your AUCt/AUCinf>0.8 which determines that sampling time point (extent of exposure) of and analytical method are capable enough captures appropriate elimination half life.
I believe that one another alternative could be to take available literature of BE and determine BE with AUC0-24. Over here- make sure that AUC0-24/AUCinf>0.8 for that literature and justify that lowering the LLOQ may not be useful as you have already meet the regulatory requirement.
Kindly go through- doi:10.1002/cpdd.866. As per the article, the mean profile is given below:

[image]

The GMR along with 90% CI is given below:

[image]

Although you may not have individual data, make a point that AUC0-24/AUCinf>0.8.
Ideally you are meeting the regulatory requirement.
Regards,
Dshah

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