Difference between actual and published PK parameters [Study As­sess­ment]

posted by Helmut Homepage – Vienna, Austria, 2022-02-14 18:30 (790 d 18:56 ago) – Posting: # 22780
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Hi Loky do,

❝ A inquiry from the Authority …

Out of curiosity: Which one? :-D

❝ … stating that the LLOQ of the study is not sensitive enough for accurate measuring of volunteers concentrations as the drug was detected (appear concentrations) for only 24 hours in most of the volunteers.

Why the heck? You covered more than 80% of AUC0–∞.

❝ What is the possible causes for the difference between the actual and the published t1/2?

No idea. More common are cases like this one (slides 16–21), i.e., due to a more sensitive method the half life is longer than reported in literature. If your method was validated, I don’t see any reason to question the outcome of the study.

❝ in addition to practically when we extend the calibration curve in order to measure all volunteers concentrations, it doesn't much differ from the old result?

That would require a least a partial revalidation.
BTW, method validation should not be considered as an end in itself. It serves a purpose. You were already able to describe the extent of absorption sufficiently enough. IMHO, it would be just a waste of time, resources, and money only to bring the extrapolated AUC down to say, <5% instead of <20%.

❝ Also what would be the proper justification and the action to be taken in response to the authority?

I’m not good in diplomatic answers to stupid questions. Sorry.

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