PBPK model input parameters for sonidegib
| Parameter | Value |
|---|---|
| Physical chemistry and blood binding | |
| Molecular weight (g/mol) | 485.5 |
| logP | 4.26 |
| pKa | 4.2 |
| B/P | 0.55 |
| fu,plasma | 0.025 |
| Absorption | |
| Model used | First order |
| fa | 0.3 (200 mg); 0.15 (800 mg) |
| Lag time (h) | 1 |
| ka (per h) | 0.57 |
| Peff,man (×10−4 cm/s) | 2 |
| fugut | 1 |
| Qgut (l/h) | 9.086 |
| Distribution | |
| Model used | Full PBPK |
| Vss (l/kg) | 22.7 |
| Elimination | |
| Model used | Enzyme kineticsa |
| CLint CYP3A4 (µl/min/pmol CYP) | 0.687 (0.417 cancer patients) |
| Additional HLM CLint (µl/min/mg protein) | 31.38 (19.06 cancer patients) |
| CLR (l/h) | 0 |
B/P, blood to plasma ratio; fu,plasma, fraction unbound in the plasma.
↵a The CLint values were estimated using the Simcyp retrograde model; see Materials and Methods.