DDI predictions of MVC with inhibitors and inducers
Simcyp default files for inhibitors were used (Sim-Ketoconazole-400 mg QD, SV-Ritonavir, SV-Efavirenz, and SV-Rifampicin-MD).
| MVC DDI with | Interactions in Model | Predicted AUCR | Observed AUCR (90% CI) | Rpred/obs | References for Observed |
|---|---|---|---|---|---|
| TVR 750 mg (three times a day) | CYP3A (inh, TDI), OATP1B1, P-gp | 7.90 | 9.49 (7.94, 11.34) | 0.83 | Vourvahis et al. (2014) |
| Ketoconazole 450 mg (once a day) | CYP3A (inh), P-gp | 4.04 | 5.01 (3.98, 6.29) | 0.81 | Abel et al. (2008b) |
| Ritonavir 100 mg (twice a day) | CYP3A (TDI, ind), P-gp | 3.10 | 2.61 (1.92, 3.56) | 1.1 | Abel et al. (2008b) |
| Efavirenz 600 mg (once a day) | CYP3A (ind) | 0.71 | 0.49 (0.41, 0.57) | 1.4 | Abel et al. (2008a) |
| Rifampicin 600 mg (once a day)a | CYP3A (inh, ind), OATP1B1, P-gp (ind) | 0.37 | 0.33 (0.28, 0.38) | 1.1 | Abel et al. (2008a) |
CI, confidence interval; ind, induction; inh, inhibition.
↵a The scaling factor for intestinal P-gp (×4) was assumed to induce P-gp in gut. The Ki,OATP1B1, CYP3A Emax, and CYP3A EC50 values were used from a previous report (Varma et al., 2013).