CYP2C8 Reversible Not anticipated (R-value 1.0160); lack of inhibitor; safety signals in patients taking loperamide IC50 = 13 and zopiclone µM CYP3A4 Minimally Unlikely to be relevant based on induced with ritonavir (see below) (approx.. one the effect of rifampin) UGT1A1 IC50 = 3.6 Unlikely (clinical showed 34% decrease µM in raltegravir exposure with the 3DAA regimen, but individual contribution unknown) P-gp IC50 = 38.1 Likely in intestine only ([I2]/IC50 > 10) 60 µM BCRP IC50 = 0.59 ([I2]/IC50 > 10 and [I1]/IC50 > 0.160 to 14.4 µM IC50 = 0.031 Likely (R-value 1.88 to 3.07) 60 µM Clinical study showed increased rosuvastatin & pravastatin exposure with the 3DAA regimen, but individual contribution unknown IC50 = 0.017 Likely (R-value 2.60 to 4.77) 60 µM Clinical study showed increased rosuvastatin & pravastatin exposure with the 3DAA regimen, but individual contribution unknown CYP3A4 Potent Kinetic booster for paritaprevir; will have inhibitor clinical implications for all co-administered CYP3A4 substrates; This inhibitory effect is likely to dominate over slight induction effect of paritaprevir P-gp IC50 = 0.35 Possible, but individual contribution of µM (vesicle), ritonavir to P-gp and BCRP inhibition in the > 50 µM (cell 3DAA regimen is difficult to discern BCRP IC50 = 24 µM (vesicle), 66 µM (cell based)
CYP2C8 Reversible inhibitor; IC50 = 13 µM Not anticipated (R-value 1.0160); lack of safety signals in patients taking loperamide and zopiclone CYP3A4 Minimally induced (approx.. one the effect of rifampin) Unlikely to be relevant based on with ritonavir (see below) UGT1A1 IC50 = 3.6 µM Unlikely (clinical showed 34% decrease in raltegravir exposure with the 3DAA regimen, but individual contribution unknown) P-gp IC50 = 38.1 µM Likely in intestine only ([I2]/IC50 > 10) 60 BCRP IC50 = 0.59 to 14.4 µM ([I2]/IC50 > 10 and [I1]/IC50 > 0.160 IC50 = 0.031 µM Likely (R-value 1.88 to 3.07) 60 Clinical study showed increased rosuvastatin & pravastatin exposure with the 3DAA regimen, but individual contribution unknown IC50 = 0.017 µM Likely (R-value 2.60 to 4.77) 60 Clinical study showed increased rosuvastatin & pravastatin exposure with the 3DAA regimen, but individual contribution unknown CYP3A4 Potent inhibitor Kinetic booster for paritaprevir; will have clinical implications for all co-administered CYP3A4 substrates; This inhibitory effect is likely to dominate over slight induction effect of paritaprevir P-gp IC50 = 0.35 µM (vesicle), > 50 µM (cell Possible, but individual contribution of ritonavir to P-gp and BCRP inhibition in the 3DAA regimen is difficult to discern BCRP IC50 = 24 µM (vesicle), 66 µM (cell based)