Bioequivalence and Bioavailability Forum

Hi Mittyri,

❝ Do I understand it right, that at least 3 points should be planned after the ending of absorption? What kind of parameters should I take into account for sampling time calculation?

Talking about when absorption ends makes little sense I think. You satisfy regulators by being able to characterise well the first 80% of the entire concentration/time-curve. For that purpose you should have 3 points or more in the elimination phase.

❝ For example: according to the literature data the absorption ends up in 20h, so should we add at least 3 timepoints after 20h to be able to calculate the terminal rate constant?

No that's not really it. Absorption, distribution, metabolism and elimination and distribution all happen simultaneously. As above your goal is to have 3+ points in the terminal elimination phase. And note with some APIs you may have apparent bi- or trimodel elimination so you should focus on the last of the elimiation phases. Plenty points well beyond Tmax is a good idea.

❝ I'm unable to make head nor tail of different types of halflives

❝ We have halflife of API (derived from IV profile in originator's studies), halflife of prolonged release formulation (from other BEQ studies), apparent halflife (from originator's PK studies).

❝ Which type of halflife should be used for washout calculation?

Yeah its a mess of sorts. If you work on a CR formulation then the half-life you see is not the half-life you can compare to what you get from an IV study and that may in turn be different from IR formulation half-lives. Compare to the formulation that resembles your own.
Be aware of genetic variation. Use common sense. Give a little more info, please, then we'll have a look