TABLE 1.
Parameters required for PBPK model establishment.
| Parameter type | Value | Source |
|---|---|---|
| Species information | ||
| Individual | ||
| Species | Human | — |
| Race | East Asian | — |
| Gender | Male | — |
| Endothelal Surface areas | Organ Vasculrization | PK-Sim standard |
| Body surface area | Mosteller | PK-Sim standard |
| Age (years) | 25.7 | Project mean |
| Weight (kg) | 60.98 | Project mean |
| Height (cm) | 167.60 | Project mean |
| BMI | 21.71 | Project mean |
| Population | ||
| Age (years) | 18–60 | Simulation setting |
| Number of individuals | 100 | Simulation setting |
| Proportion of females | 50% | Simulation setting |
| Drug information | ||
| Physiochemical properties | ||
| log P | 0.4 (Drugbank) | Optimized value: 0.43 |
| 0.421 (ADMETlab) | PK-Sim optimization | |
| 0.935 (ADMETlab 2.0) | ||
| 1.38 (SwissADME) | ||
| 1.57 (ADMESAR) | ||
| fu (plasma) | 18% (Drugbank) | Drugbank |
| 28.64% (ADMETlab 2.0) | ||
| 33.306% (ADMETlab) | ||
| Moleculr weight | 170.23 | Drugbank |
| pka (Strongest Acidic) | 8.09 | Drugbank |
| pka (Strongest Basic) | -2.9 | Drugbank |
| Solublity (mg/L) | 1,200 (Drugbank) | Drugbank |
| 1,531.278 (ADMETlab) | ||
| 234 (SwissADME) | ||
| Absorption | ||
| Specific intestinal permeability (cm/min) | 3.92x10−6 | Thelen et al. (2011) |
| Distribution | ||
| Specific organ permeability (cm/min) | 3.18x10−3 | Willmann et al. (2005) |
| Metabolism and Elimination | ||
| Total clearance (L/h) | 4.42–13.5 | Pan et al. (2001); Tang. et al. (2002); Mendes et al. (2014); Główka et al. (2018) |
| Optimized value: 9 | ||
| PK-Sim optimization | ||
| Total clearance (L/h/kg) | 0.07–0.22 | — |
| Total hepatic clearance (L/h/kg) | 0.09 | PK-Sim optimization |
| Hepatic specific clearance (1/min) | 0.36 | PK-Sim calculation |
| Renal clearances (L/h/kg) | 0.05 | PK-Sim optimization |
| Renal specific clearance (1/min) | 0.70 | PK-Sim calculation |
| Dosing Information | ||
| Administration type | Oral | — |
| Dose (mg) | 50 | — |
| Dosing interval | Single | — |
| Formulations | Dissolved | PK-Sim standard |