Predicted net effect vs. observed AUC ratios and associated geometric fold error assuming unbound plasma concentrations and interaction in the liver only ( eq. 9 ) and interaction in the liver plus intestine ( eq. 16 )
Precipitant | Range of DDI (Observed) | [I]H, u | AUC′/AUC (Predicted) [I]H,u | GFE | AUC¢/AUC (Predicted) [I]H,u + [I]G | GFE |
|---|---|---|---|---|---|---|
| μM | ||||||
| Avasimibe | 0.27 | 0.001 | 1.00 | 3.7 | 1.4 | 5.2 |
| Avasimibe | 0.06 | 0.003 | 0.99 | 17 | 1.7 | 29 |
| Azithromycin | 0.87–1.3 | 0.193 | 1.2 | 1.1 | 2.0 | 1.8 |
| Azithromycin | 1.0 | 0.193 | 1.2 | 1.2 | 1.5 | 1.5 |
| Bosentan | 0.66 | 0.091 | 0.51 | 1.3 | 0.38 | 1.7 |
| Carbamazepine | 0.26 | 8.50 | 0.19 | 1.4 | 0.1 | 2.4 |
| Cimetidine | 1–2.2 | 2.58 | 1.1 | 1.5 | 1.7 | 1.1 |
| Clarithromycin | 3.6 | 1.30 | 5.8 | 1.6 | 10 | 2.8 |
| Clarithromycin | 5.5–8.4 | 1.62 | 6.5 | 1.1 | 11 | 1.6 |
| Clarithromycin | 5.3 | 1.19 | 5.6 | 1.1 | 7.4 | 1.4 |
| Clarithromycin | 10 | 2.59 | 8.1 | 1.2 | 12 | 1.2 |
| Cyclosporine | 8.0 | 0.193 | 2.4 | 3.3 | 3.7 | 2.2 |
| Cyclosporine | 2.6 | 0.058 | 1.5 | 1.7 | 2.2 | 1.2 |
| Diltiazem | 3.8 | 0.035 | 2.9 | 1.3 | 5.0 | 1.3 |
| Diltiazem | 3.0 | 0.035 | 2.9 | 1.0 | 3.7 | 1.2 |
| Diltiazem | 4.8 | 0.068 | 4.2 | 1.2 | 6.3 | 1.3 |
| Diltiazem | 2.3–3.4 | 0.035 | 2.9 | 1.0 | 3.8 | 1.4 |
| Erythromycin | 3.3 | 0.101 | 1.5 | 2.2 | 2.7 | 1.2 |
| Erythromycin | 3.8–4.4 | 0.219 | 2.1 | 2.0 | 3.7 | 1.1 |
| Erythromycin | 3.8 | 0.219 | 2.1 | 1.8 | 2.8 | 1.4 |
| Erythromycin | 6.2 | 0.219 | 2.1 | 3.0 | 3.2 | 2.0 |
| Erythromycin | 2.1 | 0.754 | 4.2 | 2.0 | 5.5 | 2.6 |
| Ethinyl estradiol | 1.1–1.2 | 0.010 | 1.0 | 1.1 | 1.7 | 1.4 |
| Fluconazole | 3.6 | 6.41 | 1.8 | 2.0 | 3.0 | 1.2 |
| Fluconazole | 3.6–4.9 | 26.2 | 3.8 | 1.1 | 6.5 | 1.5 |
| Fluconazole | 2.7 | 19.6 | 3.2 | 1.2 | 4.0 | 1.5 |
| Fluconazole | 2.1–4.4 | 6.41 | 1.8 | 1.8 | 2.3 | 1.4 |
| Fluoxetine | 0.87 | 0.029 | 1.2 | 1.3 | 2.1 | 2.4 |
| Fluoxetine | 1.0 | 0.029 | 1.2 | 1.2 | 1.6 | 1.6 |
| Itraconazole | 6.2–10.8 | 0.004 | 1.4 | 5.7 | 2.4 | 3.2 |
| Itraconazole | 10 | 0.004 | 1.4 | 7.2 | 2.1 | 4.7 |
| Itraconazole | 3.1–4.5 | 0.004 | 1.4 | 2.8 | 1.9 | 2.1 |
| Ketoconazole | 14 | 0.054 | 4.2 | 3.2 | 7.4 | 1.8 |
| Ketoconazole | 5.2–8.7 | 0.019 | 2.3 | 2.9 | 4.0 | 1.7 |
| Ketoconazole | 9.5–15.9 | 0.028 | 2.9 | 4.4 | 4.3 | 2.9 |
| Ketoconazole | 9.2–22.4 | 0.054 | 4.2 | 3.6 | 5.6 | 2.7 |
| Mibefradil | 8.9 | 0.041 | 8.9 | 1.0 | 16 | 1.8 |
| Mibefradil | 8.4 | 0.041 | 8.9 | 1.1 | 12 | 1.4 |
| Modafinil | 0.42 | 19.6 | 0.22 | 1.9 | 0.28 | 1.5 |
| Nafcillin | 0.37 | 4.84 | 0.37 | 1.0 | 0.48 | 1.3 |
| Nelfinavir | 6.1 | 0.106 | 4.2 | 1.4 | 10 | 1.6 |
| Nifedipine | 1.0 | 0.015 | 0.97 | 1.1 | 0.44 | 2.4 |
| Phenobarbital | 0.39 | 26.0 | 0.13 | 2.9 | 0.16 | 2.4 |
| Phenytoin | 0.06 | 5.25 | 0.27 | 4.5 | 0.19 | 3.2 |
| Pioglitazone | 0.98 | 0.028 | 1.00 | 1.0 | 1.5 | 1.6 |
| Pleconaril | 0.65 | 0.024 | 0.93 | 1.4 | 0.13 | 4.8 |
| Raloxifene | 1.0 | 0.00005 | 1.0 | 1.0 | 1.8 | 1.8 |
| Rifampin | 0.016–0.041 | 2.38 | 0.11 | 4.0 | 0.09 | 3.0 |
| Rifampin | 0.08 | 2.38 | 0.11 | 1.4 | 0.13 | 1.6 |
| Rifampin | 0.09–0.14 | 2.38 | 0.11 | 1.0 | 0.10 | 1.2 |
| Rifampin | 0.05 | 2.38 | 0.11 | 2.2 | 0.12 | 2.4 |
| Ritonavir | 20.4–40.7 | 0.176 | 14 | 2.0 | 19 | 1.5 |
| Rosiglitazone | 0.88 | 0.001 | 1.0 | 1.1 | 1.2 | 1.4 |
| Roxithromycin | 1.5 | 0.718 | 1.6 | 1.1 | 2.8 | 1.9 |
| Saquinavir | 5.2 | 0.009 | 6.3 | 1.2 | 12 | 2.3 |
| Troglitazone | 0.62 | 0.041 | 5.3 | 8.6 | 8.7 | 14 |
| Troleandomycin | 3.8 | 0.006 | 1.1 | 3.5 | 1.7 | 2.3 |
| Verapamil | 2.9 | 0.013 | 1.3 | 2.2 | 3.5 | 1.2 |
| Verapamil | 4.7 | 0.013 | 1.3 | 3.5 | 3.0 | 1.6 |
| Geometric mean fold error |
|
|
| 1.9 |
| 2.0 |
Values highlighted in bold are above 2-fold