Bioequivalence and Bioavailability Forum

Mr Schuetz!

❝ Correct, but enterohepatic recirculation leads to secondary peaks – not drops.

Yes, of course. I mean exactly that... the peaks can create a triangulation point. Imagine that in the elimination bit, when the drug is almost eliminated, a reabsortion occurs, then it could cause a triangulation.

❝ It is a pity that some statisticians have limited knowledge of PK.

Oh yes, for sure. Also a pity that pharmacokineticists have limited knowledge of stats, and that clinical experts have limited knowledge of stats or analytics, and so on. We could go all day on this... That's why we assemble a team to plan together a study.

But we have to keep in mind that this is not a question of PK exclusively, since there are more fields of knowledge involved here. For instance, as Weidson said in his post, these points could be mistakes from clinical and/or analytical stages, or nature of the drug. I don't think is good to "ignore" statistics principles based on something that we think does not make "pharmacokinetic sense".

❝ Yes, but that’s a different story. If the measured concentration equals the baseline, you get after subtraction a “true” zero. Such values are valid and should be used. If C <LLOQ then force it to zero.

That is in fact another discussion... and a very long one. When the corrected concentration results in a negative value it makes no sense IMHO, and they ask us to force this point to zero... That's a conversation for another time.

Tks for the response!

Lucas