Induction DDIs with AUC ratios ≤0.2, NME as substrate
Drugs were orally administered; in all DDIs, rifampin was used as the inducer except for grazoprevir, where efavirenz was the inducer.
| Victim Drug | Main Enzymes/Transporters Possibly Involved | AUC Ratio | Reference |
|---|---|---|---|
| Isavuconazonium sulfate | CYP3A, butyrylcholinesterase | 0.03 | FDA (2015e) |
| Eliglustat | CYP3Aa | 0.04 (PMs) | FDA (2014c) |
| Flibanserin | CYP3A, CYP2C19 | 0.04 | FDA (2015a) |
| Ibrutinib | CYP3Aa | 0.08 (PBPK) | FDA (2013g) |
| Eliglustat | CYP3Aa | 0.09 (IMs) | FDA (2014c) |
| Eliglustat | CYP3Aa | 0.10 (EMs) | FDA (2014c) |
| Naloxegol | CYP3Aa | 0.11 | FDA (2014h) |
| Olaparib | CYP3Aa | 0.11 | FDA (2014g) |
| Rolapitant | CYP3A | 0.12 | FDA (2015o) |
| Suvorexant | CYP3A | 0.12 | FDA (2014b) |
| Tasimelteon | CYP3Aa,b | 0.14 | FDA (2014f) |
| Palbociclib | CYP3Aa | 0.15 | FDA (2015h) |
| Cobimetinib | CYP3Aa | 0.17 (PBPK) | FDA (2015d) |
| Grazoprevir | CYP3Ac | 0.17 | FDA (2016d) |
| Velpatasvir | CYP2B6, CYP2C8, CYP3A, P-gp, BCRP | 0.19 | FDA (2016b) |
| Netupitant | CYP3A | 0.20 | FDA (2014a) |
EM, extensive metabolizer; IM, intermediate metabolizer; PM, poor metabolizer.
↵a Also a substrate of P-gp based on in vitro results; induction of P-gp might contribute to the observed interaction.
↵b Also metabolized by CYP1A2, CYP2C9, and CYP2C19; rifampin is an inducer of multiple P450s.
↵c Also a substrate of P-gp and BCRP based on in vitro results; induction of P-gp and BCRP might contribute to the observed interaction.