Inhibition DDIs with AUC ratios ≥5, NME as substrate
Drugs were orally administered unless specified.
| Victim Drug | Inhibitor | Main Enzymes/Transporters Possibly Involved | AUC Ratio | Reference |
|---|---|---|---|---|
| Paritaprevir | Ritonavir | CYP3A, P-gp, BCRP, OATP1B1/3 | 47.43 | FDA (2014m) |
| Eliglustat | Ketoconazole/paroxetine | CYP3A, CYP2D6a | 37.85 (PBPK in EMs) | FDA (2014c) |
| Eliglustat | Paroxetine | CYP2D6 | 28.40 (UMs) | FDA (2014c) |
| Ibrutinib | Ketoconazole | CYP3A | 23.90 | FDA (2013g) |
| Eliglustat | Fluconazole/terbinafine | CYP3A, CYP2D6 | 19.31 (AUC0–24 h, PBPK in EMs) | FDA (2014c) |
| Grazoprevir | Cyclosporine | OATP1B1/3b | 15.25 (AUC0–24 h) | FDA (2016d) |
| Grazoprevir | Lopinavir/ritonavir | CYP3A, OATP1B1/3b | 12.87 | FDA (2016d) |
| Naloxegol | Ketoconazole | CYP3Aa | 12.42 | FDA (2014h) |
| Grazoprevir | Atazanavir/ritonavir | CYP3A, OATP1B1/3b | 10.56 | FDA (2016d) |
| Grazoprevir | Rifampin (i.v.) | OATP1B1/3 | 10.22 | FDA (2016d) |
| Eliglustat | Paroxetine | CYP2D6 | 10.00 (EMs) | FDA (2014c) |
| Dasabuvir | Gemfibrozil | CYP2C8 | 9.90 | FDA (2014m) |
| Eliglustat | Ketoconazole/paroxetine | CYP3A, CYP2D6a | 9.81 (PBPK in IMs) | FDA (2014c) |
| Ibrutinib | Erythromycin | CYP3A | 8.60 (PBPK) | FDA (2013g) |
| Grazoprevir | Rifampin | OATP1B1/3b | 8.37 | FDA (2016d) |
| Ivabradine | Josamycin | CYP3Aa | 7.70 | FDA (2015c) |
| Ivabradine | Ketoconazole | CYP3Aa | 7.70 | FDA (2015c) |
| Eliglustat | Fluconazole | CYP3A | 7.54 (PBPK in PMs) | FDA (2014c) |
| Grazoprevir | Darunavir/ritonavir | CYP3A, OATP1B1/3b | 7.49 | FDA (2016d) |
| Simeprevir | Ritonavir | CYP3Aa | 7.18 | FDA (2013i) |
| Tasimelteon | Fluvoxamine | CYP1A2c | 6.87 | FDA (2014f) |
| Pirfenidone | Fluvoxamine | CYP1A2 | 6.81 (smokers), 3.97 (nonsmokers) | FDA (2014d) |
| Cobimetinib | Itraconazole | CYP3Aa | 6.62 | FDA (2015d) |
| Simeprevir | Erythromycin | CYP3Aa | 6.54 | FDA (2013i) |
| Flibanserin | Fluconazole | CYP3A, CYP2C19 | 6.41 | FDA (2015a) |
| Venetoclax | Ketoconazole | CYP3A, P-gp | 6.40 | FDA (2016e) |
| Eliglustat | Ketoconazole | CYP3Aa | 6.22 (PBPK in PMs) | FDA (2014c) |
| Ibrutinib | Diltiazem | CYP3A | 5.50 (PBPK) | FDA (2013g) |
| Isavuconazonium sulfate (prodrug) | Ketoconazole | CYP3A, butyrylcholinesterase | 5.22 | FDA (2015e) |
| Eliglustat | Paroxetine | CYP2D6 | 5.20 (IMs) | FDA (2014c) |
EM, CYP2D6 extensive metabolizer; IM, CYP2D6 intermediate metabolizer; PM, CYP2D6 poor metabolizer; UM, CYP2D6 ultrarapid metabolizer; i.v., intravenously.
↵a Also a substrate of P-gp based on in vitro results; inhibition of P-gp might contribute to the observed interaction.
↵b Also a substrate of P-gp and BCRP based on in vitro results.
↵c Also metabolized by CYP3A, CYP2C9, and CYP2C19; fluvoxamine inhibits these P450s.