Summary of Simcyp parameters for the in silico estimation of the drug interaction potential of AMG 853 both as a victim (versus ketoconazole) or a perpetrator (versus paclitaxel, rosiglitazone, or montelukast
Values in parentheses indicate the 5th and 95th percentiles for the predicted changes in AUC and Cmax.
| Victim Drug | Effector Drug | Proposed Interaction | Predicted Fold Change in AUC | Predicted Fold Change in Cmax |
|---|---|---|---|---|
| AMG 853 (200 mg) | Ketoconazole (200 mg) | Inhibition of CYP3A-mediated metabolism of AMG 853 by ketoconazole | 1.91 ± 0.18 (1.63–2.10) | 1.90 ± 0.39 (1.87–2.12) |
| Paclitaxel (4.5 mg) | AMG 853 (200 mg) | Inhibition of CYP2C8-mediated paclitaxel metabolism by AMG 853 | 1.01 ± 0.005 (1.00–1.02) | 1.01 ± 0.003 (1.00–1.03) |
| Rosiglitazone (4 mg) | AMG 853 (200 mg) | Inhibition of CYP2C8-mediated rosiglitazone metabolism by AMG 853 | 1.00 ± 0.001 (0.99–1.02) | 1.01 ± 0.004 (1.00–1.03) |
| Montelukast (4 mg) | AMG 853 (200 mg) | Inhibition of CYP2C8-mediated montelukast metabolism by AMG 853 | 1.01 ± 0.008 (1.00–1.02) | 1.01 ± 0.007 (1.00–1.02) |