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.