Table 2.
The input parameters for the tegoprzan-M1 PBPK model.
| Parameters | Initial Value | Input Value | Source |
|---|---|---|---|
| Phys-chem properties | |||
| Molecular weight (g/mol) | 373.36 | 373.36 | Predicted using ChemAxon |
| LogP | 2.1 | 2.1 | Predicted using ChemAxon |
| Compound type | Monoprotic base | Monoprotic base | |
| pKa | 5.35 | 5.35 | Predicted using ChemAxon |
| B/P | 1.116 | 1.116 | Predicted in SimCYP® |
| fu | 0.257 | 0.257 | Predicted in SimCYP® |
| Distribution | |||
| Distribution model | Minimal PBPK | Minimal PBPK | |
| Vss (L/kg) | - | 1.72 | Parameter estimation |
| kin (h−1) | - | 40 | Parameter estimation |
| kout (h−1) | - | 7.76 | Parameter estimation |
| Vsac (L/kg) | - | 1.23 | Parameter estimation |
| Prediction model | Method 2 (Rodgers and Rowland model) |
Method 2 (Rodgers and Rowland model) |
|
| Elimination | |||
| Clearance type | WOMC | WOMC | |
| CLint,HLM (μL/min/mg protein) | 2.353 | 2.353 | Experimental data |
| CLint,HLC (μL/min/mg protein) | - | 3.15 | Parameter estimation |
| CLR (L/h) | 1.1 | 1.1 | Assumed that same with parent |
| Additional systemic clearance (L/h) | - | 1.44 | Parameter estimation |
fu: unbound fraction in plasma; Vss: volume of distribution in steady state; kin: input rate constant for single adjusting compartment; kout: elimination rate constant for single adjusting compartment; Vsac: volume of single adjusting compartment; WOMC: whole-organ metabolic clearance; HLC: human liver cytosol; HLM: human liver microsomes; CLint: intrinsic clearance; CLR: renal clearance.