Bioequivalence and Bioavailability Forum

Hi Helmut,

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

Thanks! The scenario on page 20 is exactly what I am facing but the difference in t1/2 is much larger than yours (i.e. 2.5 hrs vs 4.5 hrs). It's an IR product and the drug is very old. Previous studies (from archive or literature) had a profile with a monophasic elimination phase due to sampling time and BLQ. Since I sampled longer and has a much much lower BLQ, the biphasic appearance popped up. I double checked the bioanalytical method and I didn't see any issues (calibration curves looked great, intraday and interday CVs looked great, no other issues).

❝ ❝ 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.

Maybe R2 from PHX was like .99xxx and my R2 was like .7? PHX only picked timepoints along the "2nd phase" of the curve while I picked data from more timepoints from both the 1nd phase and the 2nd phase of the elimination phase.

thx
John