Bioequivalence and Bioavailability Forum

Hi Rajasekhar,

❝ Example: Tamsulosin

❝ how to fix number of days to dosing

Until (pseudo) steady state is achieved. See this post for an example of linear PK.
Which regulation are you “targeting”? For the FDA a multiple dose study is not required. Since the SmPC recommends intake after breakfast, according to the EMA’s GL the multiple dose study has to be performed in fed state.

❝ how to fix number of doses per day

According to the posology of the reference (for tamsulosin OAD after breakfast).

❝ My regular practice is if label/smpc states achievement of steady-state concentrations by the fifth day of once-a-day dosing for Tamsulosin, i will design the study state protocol with once a day dosing for five days.

Fine but copy/paste ≠ science.

❝ […] i want to know the exact scientific rationale behind this.

Kudos. Steady state is practically reached after 5–7 predominant half lives (96.9–99.2% of theoretical steady state). Note that Flomax^® is a CR-formulation (flip-flop PK, where k_a < k_e). Whereas the elimination half life (after IV or IR) is ~6–7 hours, the apparent one of the CR is substantially prolonged (see the FDA’s NDA approval; page 217 of the PDF).

For drugs with nonlinear PK (e.g., saturation of metabolizing enzymes, auto-induction or -inhibition) it is complicated. Consult with a pharmacokineticist.