Bioequivalence and Bioavailability Forum

Hi John,

❝ What if my NCA calculated half-life of a drug is significantly longer than the literature reported half-life which is well established (and I have old study data to back up the literature half-life as well). The newly calculated half-life is longer because I sampled longer than usual and the bioanalytical method has a much lower BLQ. Note that the elimination phase also has a biphasic appearance.

See this case (slides 16–21). A very old and ‘popular’ drug.

❝ Since the data is the data, I assume there is nothing that I would need to do other than writing something to discuss why the my calculated half-life is longer?

Correct. No worries.

❝ FYI, i just let Phoenix to pick the timepoints itself to calculate the half-life. Of course I can override and select the timepoint as well but then the R2 might not be optimal.

Define “optimal”.
\(\small{R_{\text{adj}}^2}\) is just a tool and a “greedy” algorithm, since it might include too early time points. Further, it regularly fails with controlled release products (flat profiles) and multiphasic release products. Visual inspection of the fits is mandatory. In Phoenix I start with the ‘Best Fit’ algo and subsequently correct questionable start/end times. Yes, it is subjective but better than trusting in Artificial Unintelligence.
See also there and scroll down a bit. It gives also some references.

Heck, writing an article about estimating \(\small{\widehat{\mit{\lambda}}_\text{z}}\) is on my todo-list for years…