Science vs. regulations [Regulatives / Guidelines]

posted by Achievwin – US, 2020-05-08 00:59 (1500 d 13:30 ago) – Posting: # 21404
Views: 15,002

Good discussions:

❝ ❝ For reference: Tmax: 0.67, Tlast: 28.25

❝ ❝ For test: Tmax: 0.50, Tlast: 23.91

Aren't we lost in pure numbers and forgot to look at the individual curves?
In order to have accurate AUC estimations you need to have at least two measurable concentrations (non-BQL) before Tmax and as many time points as possible on either side of Tmax.

With 067 and 0.50 hours as Tmax how many blood draws you can practically take (assuming this is an oral formulation) may be we have to go to IV blood sampling schedule.

I saw somewhere blood samples were taken 24 and 48 hrs (assuming these are ambulatory samples there will be lot of time variation.), Hardly we completed 1 or 2 half lives. and we expect to cover 80% AUC?

Even assuming we covered AUC there is always some bad apples, in my experience due to some bad data points in the extremes you may tend to have all kinds of elimination patterns (positive slope, bad two many missed blood draws or BQL values… so it is not surprising that AUC% is less than 80% in more than 30% subjects what is that 30% in 12 or 18 subjects?

If i am designing study I take following precautions (everyone knowns these things but I am listing)
  1. see you heavy sampling either side of your Tmax (this covers majority of the AUC and accurately determines Cmax).

  2. Ensure you have at least two blood draws for every half life

  3. Capture blood draws up to 4 half lives, if your assay permits your half life is not long

Then a priori in the protocol SAP include limitations on reporting AUCinf and %Extrp.

Hope this helps.

Edit: Please don’t shout[Helmut]

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