Bioequivalence and Bioavailability Forum

Hi John,

❝ … why kel cannot be estimated …

<picky>

\(\begin{array}{lcl}
\color{Red}{\textsf{PK modeling}}&\longrightarrow& \widehat{k}_\text{el}\\
\color{Green}{\textsf{NCA}}&\longrightarrow&\widehat{\lambda}_\text{z}
\end{array}\)

</picky>

❝ … the Use guide lists the reasons [as to why kel cannot be estimated for a subject] but I am looking for something in the result output relevant to the subject's profile.

Not in the output.

❝ I use the best fit method for slope calculation. The semi-log plot just showed the statement "cannot be determined" or something, the "warning and error" output showed "No parameters could be extrapolated to infinity". I didnt see anything in the core output.

Right. After the “best fit” method you should check every single profile for plausibility (as not only recommended in the literature but also in the User’s Guide of PHX/WNL) and correct the selected data if necessary.
Most common cases for ‘failures’:

• Long half live and last data point close to the LLOQ results in \(\lambda_\text{z}\leq0\). Exclude the increasing concentration. Optionally select an earlier starting point.
  
• Low absorption of the drug in this subject. The profile ‘drops’ fast below the LLOQ. See the last paragraph of this post. If the half live estimated from only two data points is consistent with the others, use it.

Of course, you need an SOP for that. Even then, it could cause an assessor to frown.