Ki values obtained from reversible inhibition experiment and DDI-predicted AUC ratio (inhibition term used fromeq. 9) The values used for [I] in vivo were estimated total systemic plasma concentration.
Precipitant | DDI (Observed) | Ki | Predicted AUC′PO/AUCPO (Reversible Inhibition) | GFEa |
|---|---|---|---|---|
| μM | ||||
| Avasimibe | 0.27 | 0.80 | 1.6 | 5.8 |
| Avasimibe | 0.06 | 0.80 | 2.5 | 42 |
| Bosentan | 0.66 | 10 | 1.2 | 1.9 |
| Cyclosporine | 8.0 | 8.9 | 1.2 | 6.6 |
| Cyclosporine | 2.6 | 8.9 | 1.1 | 2.4 |
| Erythromycin | 3.3 | 13 | 1.0 | 3.2 |
| Erythromycin | 4.1 | 13 | 1.1 | 3.8 |
| Erythromycin | 3.8 | 13 | 1.1 | 3.6 |
| Erythromycin | 6.2 | 13 | 1.1 | 5.8 |
| Erythromycin | 2.1 | 13 | 1.2 | 1.7 |
| Fluconazole | 3.6 | 6.8 | 1.9 | 1.9 |
| Fluconazole | 4.3 | 6.8 | 4.1 | 1.1 |
| Fluconazole | 2.7 | 6.8 | 3.5 | 1.3 |
| Fluconazole | 3.2 | 6.8 | 1.9 | 1.7 |
| Fluoxetine | 0.87 | 5.3 | 1.1 | 1.2 |
| Fluoxetine | 1.0 | 5.3 | 1.1 | 1.1 |
| Itraconazole | 7.9 | 0.01 | 9.7 | 1.2 |
| Itraconazole | 10 | 0.01 | 9.7 | 1.0 |
| Itraconazole | 3.9 | 0.01 | 9.7 | 2.5 |
| ketoconazole | 14 | 0.012 | 14 | 1.0 |
| ketoconazole | 6.8 | 0.012 | 13 | 1.9 |
| ketoconazole | 13 | 0.012 | 14 | 1.1 |
| ketoconazole | 15 | 0.012 | 14 | 1.1 |
| Mibefradil | 8.9 | 2.3 | 1.5 | 6.0 |
| Mibefradil | 8.4 | 2.3 | 1.5 | 5.6 |
| Nelfinavir | 6.1 | 4.0 | 2.5 | 2.5 |
| Pioglitazone | 1.0 | 10 | 1.2 | 1.3 |
| Raloxifene | 1.0 | 9.9 | 1.0 | 1.0 |
| Ritonavir | 27 | 0.04 | 14 | 2.0 |
| Rosiglitazone | 0.88 | 12 | 1.0 | 1.2 |
| Saquinavir | 5.2 | 0.35 | 2.1 | 2.5 |
| Troglitazone | 0.62 | 5.0 | 1.8 | 3.0 |
| Troleandomycin | 3.8 | 1.3 | 1.1 | 3.4 |
| Geometric mean fold error |
|
|
|
3.7
|
↵ a GFE is the geometric fold error in predicting DDI (predicted/observed DDI). Values highlighted in bold are above 2-fold