AUC0-τ estimation with time deviations [NCA / SHAM]

posted by Helmut Homepage – Vienna, Austria, 2019-02-10 19:32  – Posting: # 19897
Views: 2,478

Hi Nastia,

» I'd like to understand the correct method to calculate AUC0-τ […]

Duno what is correct. Just my opinion.

» Aiming to calculate concentration at t=0, Phoenix use the minimum observed during the dose interval (from dose time to dose time+tau) for extravascular and infusion data (while for IV bolus data it performs a log-linear regression).

Ha-ha, you’ve read the manual. :-D

» That is for extravascular or infusion data in the listed dataset first point (time=0) would be replaced by 20, …

Yep, cause it is the minimum within {0, τ}. The concentration 2 at 24.5 is ignored. What a strange idea!

» … so that AUC0-τ equals 1325

By the linear trapezoidal method (dammit!)… With lin-up/log-down I get 1298.

» […] I was slightly suprised that a difference in one minute should totally change the input data: in fact we throw pre-dose concentration to the bin. Are there another methdos for handling AUC0-τ in such cases (linear extrapolation for example)?

[image]In PHX not without massive tweaks.
A linear interpolation of t0|C0 and t1|C1 would give 1.986. Much better than 20. You could ask for the concentration at τ and get 2.388 – higher than the 2 at 24.5 but the fit is not that good. Note that this value confirms what PHX reports for Ctau. 

Interesting: If you enter in the field 0 you get again 20. As designed but IMHO, stupid.

What I would do:
» There are also some more questions about AUC0-τ:
» Interval of dosing (τ, 24 hour) is always a constant for all subjects not depending for the actual dose period, isn't it?

Yes. Otherwise you would open Pandora’s box.

» What is the best way to handle with BLQ in the end of the dosing period for steady-state?

Lin-up/log-down as usual. Don’t you have any accumulation or is the method lousy? ;-)

Cheers,
Helmut Schütz
[image]

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