Sensitivity Assessment and selection of the optimal dose
The sensitivity of the model-based simulations was assessed based on its
ability to distinguish the PK profiles between different doses. Since
the doses of Mercaptopurine PFOS 10mg/mL are titrated based on body
weight or surface area, exposure linearity can also be safely assumed
within a 2-fold dose range. Therefore, only doses between 25 mg and 50
mg were simulated.
Doses of 25mg, 35mg, 37.5mg and 40 mg were simulated for the suspension
in addition to the tablet dose of 50 mg. The simulations included the
same pharmacokinetic variability of the Reference and Test products as
observed in the clinical study. The simulated profiles for the test
product corresponding to these doses were compared with the simulated
profile of Reference product and evaluated for the qualification of the
BE criterion for the extent of absorption (AUC) and the dose of the 6MP
PFOS which would match the exposure of the 6MP 50mg tablets was
selected.