Bioequivalence and Bioavailability Forum

Dear Averroes!

❝ I would like some advice on how to justify pre-dose concentration in the 2nd period, as we found them in around 50 % of subjects. It's very clear that the wash-out period was insufficient, but I would like to report that in an elegant way.

Well, nothing to justify here. Shit happens; just report it and learn from it for the next studies. A common mistake is to plan the washout on the mean half-life reported in literature. Remember that higher than expected pre-dose values may occur if there is high inter-subject variability (especially if the drug is subjected to polymorphism). Plan always for the worst case (see this presentation, slides 40-42).

❝ As far as I know it should not be critical as all of them are below 5% of Cmax. Both test and reference were affected equally.

Right. Maybe you will see a slight period effect, which will be accounted for in the ANOVA anyway. Just give it a try: Take the data of any BE study and multiply all values in the second period by let's say 100. The outcome (PE, confidence interval) will be exactly the same – although you will notice a highly significant period effect.