Summary of important mechanism-based DDI predictions and clinical observations of the 3D regimen
| Mechanism | Perpetrator | Victim | ||
|---|---|---|---|---|
| DDI Predictions | Clinical Observations | DDI Predictions | Clinical Observations | |
| CYP3A | Ritonavir | Ritonavir | ↓ 3D regimen with strong inducers | ↓ 3D regimen with carbamazepine |
| ↑ Sensitive substrates | ↑ Paritaprevir and tacrolimus | 3D regimen with strong inhibitors | 3D regimen with ketoconazole | |
| CYP2C8 | None | – | ↑ Dasabuvir with strong inhibitors | ↑ Dasabuvir with gemfibrozil |
| CYP2C19 | Ritonavir and dasabuvir | Ritonavir | None | – |
| Sensitive substratesa | ↓ Omeprazoleb | |||
| OATP1B1 and OATP1B3 | Paritaprevir | Paritaprevir | ↑ Paritaprevir with strong inhibitors | ↑ Paritaprevirb with atazanavir |
| ↑ Sensitive substrates | ↑ Pravastatin | |||
| BCRP | Paritaprevir | Paritaprevir | ↑ 3D regimen with strong inhibitors | ↑ 3D regimenb with cyclosporine |
| ↑ Sensitive substrates | ↑ Rosuvastatin | |||
| UGT1A1 | 3D regimen | 3D regimen | None | – |
| ↑ Sensitive substrates | ↑ Raltegravirb | |||
Upward arrows, downward arrows, and horizontal arrows indicate an increase, decrease, or no change in systemic exposure, respectively. Dashes indicate that the mechanism was not tested in dedicated clinical trials. Additional information on coadministered drugs with the 3D regimen: carbamazepine (strong CYP3A inducer), ketoconazole (strong CYP3A inhibitor), gemfibrozil (strong CYP2C8 inhibitor), atazanavir (OATP and CYP3A inhibitor), cyclosporine (OATP, P-gp, and BCRP inhibitor), pravastatin (OATP1B1 and OATP1B3 substrate), rosuvastatin (OATP and BCRP substrate), and raltegravir (UGT1A1 substrate).
↵a CYP2C19 induction was not considered in DDI predictions, due to unavailability of model parameters EC50 and Emax for ritonavir.
↵b The change in exposure is not clinically relevant (Badri et al., 2015; Khatri et al., 2016).