Bioequivalence and Bioavailability Forum

Dear Smart People!

I'd like to understand the correct method to calculate AUC_0-τ in the case of time deviations in the first sample point (actually I think that we always have deviations in the first point cause it is impossible to "eat" drug and "give" blood at the same time).

Suppose we have to calculate NCA parameters for multiple dose during n-th dose period of 24 hours.
We have these concentations and time deviation -1 min in the first sample and 0,5 hours in the last:
Data set 3
 Time  Conc
-0.017     1
1          60
2          80
3          100
4          130
5          160
6          130
7          100
8          90
10         70
12         40
14         30
18         20
24.5       2

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).

That is for extravascular or infusion data in the listed dataset first point (time=0) would be replaced by 20, so that AUC_0-τ equals 1325 while if we will not include 1-minute time deviation it would be 1316. May be this example is not so demonstrative but 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 AUC_0-τ in such cases (linear extrapolation for example)?

There are also some more questions about AUC_0-τ:
Interval of dosing (τ, 24 hour) is always a constant for all subjects not depending for the actual dose period, isn't it?
What is the best way to handle with BLQ in the end of the dosing period for steady-state?