Table II.
Modifications in Drug Specific Parameters of Each Individual CYP Enzyme Substrates by Model Optimization
| Parameters (unit) | Original values provided by SimCYP | Values after model optimization |
|---|---|---|
| faMidazolam | 1 | 0.9 |
| KaMidazolam (1/h) | 3 | 15 |
| VsacMidazolam (L/kg) | N/A | 0.3 |
| Q Midazolam (L/h) | N/A | 30 |
| Clint-CYP2C19-Omeprazole(μL/min/pmol of isoform) | 264 | 66 |
| Clint-CYP3A4-Omeprazole(μL/min/pmol of isoform) | 39.5 | 9.9 |
| FaS-Warfarin | 1 | 0.8 |
| KaS-Warfarin (1/h) | 1.85 | 15 |
| VsacS-Warfarin (L/kg) | N/A | 0.03 |
| Q S-Warfarin (L/h) | N/A | 0.5 |
| faCaffeine | 1 | 0.7 |
| KaCaffeine (1/h) | 2.18 | 10 |
| Clint-CYP3A4-Simvastatin(μL/min/pmol of isoform) | 2597 | 1800 |
Cl int intrinsic hepatic clearance, CYP cytochrome P450, fa fraction of absorption, ka absorption rate constant, Q distribution clearance, Vsac volume of single-adjusting compartment