Bioequivalence and Bioavailability Forum

Hi BNR,

❝ I thought AUC0-tau not reported by Phoenix is because Lambda can't be calculated.

Exactly. Works as designed. See also the “Phoenix WinNonlin 6.4 user’s Guide” ► Noncompartmental Analyis ► Partial areas
I suggest to ☑ Intermediate Output in Setup/Options-tab.
Since Phoenix 6.0 (and different to ‘classical’ WNL up to 5.3) in the automatic setup (BestFit) C_max/t_max is not included in the fitting procedure. Hence, in dataset 1 you have just two data points left and don’t get an estimate of λ_z from PHX. In the Core output you find for data set 1:

Calculation method:  Linear Trapezoidal Rule for for Increasing Values,
                     Log Trapezoidal Rule for Decreasing Values
Weighting for lambda_z calculations:  Uniform weighting
Lambda_z method:  Find best fit for lambda_z,  Log regression

Intermediate Output: Trying different time intervals to get best fit for LambdaZ
--------------------------------------------------------------------------------
  Lower_time Upper_time PtsUsed  LambdaZ      Rsq    Adj_Rsq
  ----------------------------------------------------------
  Unable to determine Lambda_z

Intermediate Output: AUC_TAU
----------------------------
Computing partial area from 0.000000 to 24.000000:

*** Warning 14530: Lambda_z could not be estimated.
No parameters could be extrapolated to infinity.

*** Warning 14531: AUC_TAU could not be estimated.
Steady state PK parameters could not be estimated.

However, for dataset 2:

Intermediate Output: Trying different time intervals to get best fit for LambdaZ
--------------------------------------------------------------------------------
  Lower_time Upper_time PtsUsed  LambdaZ      Rsq    Adj_Rsq
  ----------------------------------------------------------
     12.00      23.80      3      0.0612    0.8284    0.6568
  Best value for Lambda_z:      0.0612, and intercept:     8.0759

Intermediate Output: AUC_TAU
----------------------------
Computing partial area from 0.000000 to 24.000000:
piece from (0.000000, 1000.000000) to (4.000000, 1500.000000) = 5000.000000
piece from (4.000000, 1500.000000) to (8.000000, 1750.000000) = 6500.000000
piece from (8.000000, 1750.000000) to (12.000000, 1750.000000) = 7000.000000
piece from (12.000000, 1750.000000) to (16.000000, 1000.000000) = 5360.820879
piece from (16.000000, 1000.000000) to (23.800000, 800.000000) = 6991.015384
piece from (23.800000, 800.000000) to (24.000000, 741.073056) = 154.032169
Partial area from 0.000000 to 24.000000 = 31005.868431

PHX’s default is not a law (and the automatic method needs inspection and adjustments anyhow – search the forum for ‘TTT method’ and the references given in the posts). You could manually select the last three (or maybe even better only the last two) data points in such a case.

See also this presentation about C_min vs. C_τ where related problems exist.