Predicted net DDI vs. observed and associated geometric fold error assuming total plasma concentrations and interaction in the liver only (eq. 9) Predictions were made assuming an exclusively competitive mechanism, a TDI mechanism and a mixed mechanism.
Precipitant | DDI (Observed) | DDI Predicted (Competitive Mechanism) | GFE | DDI Predicted (TDI Mechanism) | GFE | DDI Predicted (Mixed Mechanism) | GFE |
|---|---|---|---|---|---|---|---|
| Avasimibe | 0.27 | 1.6 | 5.8 | 1.0 | 3.7 | 0.63 | 2.3 |
| Avasimibe | 0.06 | 2.5 | 42 | 1.0 | 17 | 0.60 | 10 |
| Bosentan | 0.7 | 1.2 | 1.9 | 1.0 | 1.5 | 0.09 | 7.4 |
| Carbamazepine | 0.26 | 1.0 | 4.0 | 1.0 | 3.8 | 0.09 | 2.8 |
| Ethinyl estradiol | 1.2 | 1.0 | 1.1 | 1.1 | 1.1 | 1.0 | 1.1 |
| Fluoxetine | 0.87 | 1.1 | 1.2 | 3.5 | 4.1 | 2.5 | 2.8 |
| Fluoxetine | 1.0 | 1.1 | 1.1 | 3.5 | 3.5 | 2.5 | 2.5 |
| Mibefradil | 8.9 | 1.5 | 6.0 | 14 | 1.6 | 14 | 1.5 |
| Mibefradil | 8.4 | 1.5 | 5.6 | 14 | 1.7 | 14 | 1.6 |
| Modafinil | 0.42 | 1.0 | 2.5 | 1.0 | 2.4 | 0.19 | 2.2 |
| Nafcillin | 0.4 | 1.0 | 2.8 | 1.0 | 2.7 | 0.24 | 1.5 |
| Nelfinavir | 6.1 | 2.5 | 2.5 | 14 | 2.3 | 12 | 2.0 |
| Nifedipine | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 0.71 | 1.5 |
| Phenobarbital | 0.39 | 1.0 | 2.7 | 1.0 | 2.6 | 0.10 | 3.9 |
| Phenytoin | 0.06 | 1.1 | 18 | 1.0 | 17 | 0.11 | 1.8 |
| Pioglitazone | 0.98 | 1.2 | 1.3 | 5.5 | 5.6 | 2.2 | 2.2 |
| Pleconaril | 0.7 | 1.0 | 1.5 | 1.0 | 1.5 | 0.17 | 3.9 |
| Rifampin | 0.03 | 1.0 | 36 | 1.0 | 36 | 0.09 | 3.3 |
| Rifampin | 0.08 | 1.0 | 12 | 1.0 | 12 | 0.09 | 1.1 |
| Rifampin | 0.12 | 1.0 | 8.8 | 1.0 | 8.7 | 0.09 | 1.3 |
| Rifampin | 0.05 | 1.0 | 20 | 1.0 | 20 | 0.09 | 1.8 |
| Ritonavir | 27 | 13.7 | 2.0 | 14 | 1.9 | 14 | 1.9 |
| Rosiglitazone | 0.88 | 1.0 | 1.2 | 2.4 | 2.7 | 1.8 | 2.0 |
| Saquinavir | 5.2 | 2.1 | 2.5 | 14 | 2.6 | 12 | 2.3 |
| Troglitazone | 0.62 | 1.8 | 3.0 | 14 | 22 | 13 | 21 |
| Troleandomycin | 3.8 | 1.1 | 3.4 | 6.4 | 1.7 | 2.0 | 1.9 |
| Verapamil | 2.9 | 1.1 | 2.7 | 10 | 3.5 | 3.3 | 1.2 |
| Verapamil | 4.7 | 1.1 | 4.4 | 10 | 2.2 | 3.3 | 1.4 |
| Geometric mean fold error |
|
|
7.1
|
|
6.7
|
|
3.2
|
Values highlighted in bold are above 2-fold