Bioequivalence and Bioavailability Forum

Hi Helmut,

Just following up on this discussion here, although as you say
Pharsight's Extranet is probably the better location, note my high-lighting of the last statement.

❝ Now for the interesting question: Why is WNL/PHX not calculating Ae_inf?

and also

❝ Extrapolation of urine data in NCA is a nasty business anyhow - whatever method you apply. If ever possible, stay with Ae_0-t only.

I would concur that extrapolation of urine data using NCA is extremely tricky due in major part to the difficulty of obtaining sufficient quality collection volumes to actually plot a useful profile. In my experience the use of urinary data has decreased markedly in Phase I trials over the last 10+ years, presumably as analytical techniques have become that much more sensitive to lower concentrations in plasma etc. This leads me to two questions:

1. beyond assessing metabolism pathways, is there a use for NCA of urine data; wouldn't this be more appropriate to model and fit if you truly want to understand your compound better?
   
2. the more important one, when wearing a Pharsight hat, is whether there is any benefit to the WNL user / general PK community of Phoenix implementing the extrapolation Herr Doktor Rotter described in TopFit if experience of real data shows us that this is rarely possible with confidence?

❝ 1. Calculate regression line of the terminal part of excretion rates to obtain lambda_Z

❝ 2. calculate excretion rate at t_last from that regression line

❝ 3. Ae(inf) := Ae(t_last) + excretion_rate((t_last)/lambda_Z

If people believe it is, it can be written up as an enhancement request.