Normalized sensitivity coefficients for selected parameters of 1’-OH midazolam PBPK model in sensitivity analysis with AUC and Cmax as model outputs
| Investigated Parameter | Normalized Sensitivity Coefficient | |
|---|---|---|
| AUC | Cmax | |
| Plasma protein unbound (fu,p) | 1.2 | 1.4 |
| CLint (1'-OH-MDZ → Glucuronide) | 0.9 | 0.7 |
| CLint (MDZ → 1'-OH-MDZ) | 0.1 | 0.5 |
| CLint (1'-OH-MDZ → 1,4-diOH-MDZ) | 0.05 | 0.03 |
| logP | 0.05 | 2.1 |
| Blood-to-plasma ratio (B/P) | 0.003 | 0.2 |