Bioequivalence and Bioavailability Forum

Hi Titus!

❝ This is my 1st post here and excited to learn/share science.

Welcome to the club.

❝ My study - I am carrying out Virtual BE studies for a SR-formulations and comparing its PK endpoints (Cmax, AUC).

❝ Doubt - I am confused or doubting my manually chose PK sampling time points.

❝ Drug X - Tmax - 8.40hr

❝ Therefore, I chose 12 time points (aligns with US regulatory guideline) - 1, 3, 5, 6, 7, 7.5, 8, 8.5, 9, 10, 16, and 24 hrs which covers that absorption, distribution and elimination phase of the compound.

❝ Any suggestions here to capture the PK profile the drug much better?

In BE we are interested in assessing potential differences between formulations. With SR likely you crossed the Rubicon of flip-flop PK \(\small{(k_\text{a}\le k_\text{e})}\). Thus, what you see in the late part of the profile represents absorption (not elimination). The extent of absorption of SR formulations has to be primarily assessed based on AUC_0–∞ (not on AUC_0–t). 12 time points are probably too few – esp. in the late part of the profile – in order to obtain a reliable estimate of λ_z because you need at least three time points where the profile is log-linear.

Do you know more about the drug than its t_max? Further, t_max = 8.4 h is not set in stone. Profiles of SR formulations are sometimes pretty flat. C_max is a composite PK metric (depends not only on \(\small{k_\text{a}}\) but also on \(\small{k_\text{e}}\) and \(\small{f}\)) and therefore, a poor predictor of \(\small{k_\text{a}}\). Since \(\small{k_\text{a}}\) varies between subjects, I would add more sampling time points around the anticipated t_max.