Difference between actual and published PK parameters [Study As­sess­ment]

posted by Loky do – Egypt, 2022-02-14 16:06 (91 d 03:30 ago) – Posting: # 22779
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We have a Dapoxetine Bioequivalence study up to our knowledge, Dapoxetine known to have biphasic half-life; initial and terminal half-life, with plasma levels less than 5% of peak concentrations by 24 hours post-dose, The published value for initial half-life is 1.3-1.5 hours and terminal half-life is approximately 15-19 hours.

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

A inquiry from the Authority on the study 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.

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

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

Thanks in advance

Edit: Category changed; see also this post #1[Helmut]

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