Metabolism-based clinically significant inhibitions, NMEs as substrates or perpetrators
| Victim Drug (Dose) | Inhibitor (Dose) | Enzyme(s) Possibly Involved | Max AUC Ratio | Study Design/Population | Reference |
|---|---|---|---|---|---|
| Ibrutiniba (120 mg alone, 40 mg with ketoconazole) | Ketoconazole (400 mg once daily 6 days) | CYP3A | 23.9 (dose-normalized) | One-sequence/18 healthy subjects | (FDA, 2013j) |
| Simeprevira (150 mg once daily 7 days) | Erythromycin (500 mg 3 times daily 6.5 days) | CYP3Ab | 6.5 | Random Crossover/24 healthy subjects | (FDA, 2013r) |
| Ospemifenea (60 mg SD) | Fluconazole (400 mg on Day 1; 200 mg once daily 7 days) | CYP3A, CYP2C9, CYP2C19 | 2.8 | Random Crossover/14 postmenopausal healthy women | (FDA, 2013t) |
| Riociguata (dose not available, SD) | Ketoconazole (400 mg once daily repeated doses) | CYP3Ab | 2.5 | Not provided/healthy subjects | (FDA, 2013a) |
| Vortioxetinea (10 mg once daily 28 days) | Bupropion (75 mg twice daily Day 1-3; 150 mg twice daily 11 days) | CYP2D6 | 2.3 | One-sequence/24 healthy subjects | (Chen et al., 2013; FDA, 2013e) |
| Macitentana (10 mg SD) | Ketoconazole (400 mg once daily 24 days) | CYP3A | 2.3 | Random Crossover/10 healthy subjects | (FDA, 2013s) |
| Atorvastatin (40 mg SD) | Simeprevira (150 mg once daily 12 days) | CYP3Ab,c | 2.2 | One-sequence/36 healthy subjects | (FDA, 2013r) |