Bioequivalence and Bioavailability Forum

Dear Dixit!

❝ […] what does the word build up exactly mean

Aka “saturation phase” (see this slide). The red line are concentrations after doses in the first period (“building up” steady state). The first profile is measured on day 5 (the fist yellow line). At the end of day 5 (120 hours) we switch directly to the other formulation (therefore, this is also called a “switch-over design”). During days 5–9 (the first green line) steady state of the second formulation is build up, whilst the first formulation is simultaneously eliminated (“washed out”). On day 10 we measure the second profile (the second yellow line). Such a design is preferable over a design with a treatment-free washout (days 6–9), where we would dose on days 10–14 (represented by the second green line) and measure the second profile on day 14 (the third yellow line). The duration of the study is shorter and chances of drop-outs lower.
Rationale: According to the superposition principle of pharmacokinetics steady state is independent from previous concentrations. In other words in steady state you see the same concentrations irrespective whether you start from zero or any other concentration level. You can see this in the plot, where the thin green lines are parallel, i.e., the steady state profile in a switch-over design is identical to the one obtained in a design with a wash-out.