Enzyme | Paritaprevir | Ritonavir | Ombitasvir | Dasabuvir | M1 | 3D Regimen | ||
---|---|---|---|---|---|---|---|---|

Predicted AUCR | Predicted AUCR | Predicted AUCR | Predicted AUCR | Predicted R_{1} | Predicted cAUCR | Observed cAUCR | Predicted/ Observed | |

CYP2C9 | – | 1.17 | – | 1.01 | – | 1.17 | 0.9^{a} | 1.3 |

CYP2C19 | – | 1.02 | – | 1.00 | – | 1.02 | 0.6^{a} | 1.7 |

CYP3A4 | – | 28.2 | – | – | – | 28.2 | 57^{b} | 0.5 |

UGT1A1 | 1.04 | 1.05 | 1.00 | 1.06 | 1.03 | 1.20 | 2.4^{c} | 0.5 |

Dashes indicate that parameters were not calculated because the IC

_{50}could not be estimated due to no or low inhibition at the highest tested concentration in vitro. Predicted AUCR calculations for the reversible P450 inhibition using the mechanistic static model are described in eq. 1. The predicted R_{1}calculation is from a modified basic model for predicting reversible P450 inhibition: R_{1}= 1 + [I]/*K*_{i}, where [*I*] is the unbound*C*_{max}of the inhibitor and*K*_{i}(or IC_{50}/2) is the in vitro inhibition constant. M1 is a metabolite of dasabuvir; thus, the R_{1}model was used for DDI predictions. cAUCR is the combination AUCR prediction (as described in*Materials and Methods*).↵

^{a}Menon et al. (2015).↵

^{b}Badri et al. (2015).↵

^{c}Khatri et al. (2016).