CYP3A4 substrate AUC increased by 57% when administered with ketoconazole; AUC decreased by 87% when administered with carbamazepine P-gp, P-gp substrate; Ctrough concentrations increased by 40-49% when co-administered No active uptake by with cyclosporine and atazanavir OATP1B1/3 expressed in HEK cells CYP3A4 Km2 = 71 µM; Vmax2 AUC unchanged when = 0.004 administered with ketoconazole; nmol/min/pmol; AUC decreased 30% when Km1 = 7.1 µM; Vmax1 administered with carbamazepine = 0.0001 nmol/min/pmol; CYP2C8 Km = 79.1 µM; Vmax = Unlikely 0.001 nmol/min/pmol; P-gp, Contradictory: AUC unchanged when BCRP Ombitasvir was not a administered with cyclosporine; substrate of P-gp or Cmax decreased by 23% when BCRP mediated efflux administered with atazanavir in vitro, but mice lacking these transporters had increased exposure levels CYP2C8 CYP2C8 inhibitor Confirmed (AUC increased 1025% quercetin inhibited in by gemfibrozil) vitro metabolism in human liver microsomes by 60% CYP3A4 CYP3A inhibitor Confirmed (AUC increased 42% ketoconazole by ketoconazole; decreased 70% inhibited in vitro by carbamazepine metabolism in human liver microsomes by 30% P-gp Inhibited by Confirmed C (AUC decreased 21% LY335979 and by OATP1B1 inhibitor atazanavir cyclosporin A in vitro and 30% by inhibitor cyclosporin) BCRP Inhibited by BCRP inhibitor K0143 BCRP Inhibited by BCRP M1 inhibitor
CYP3A4 substrate AUC increased by 57% when with ketoconazole; AUC decreased by 87% when with carbamazepine P-gp, P-gp substrate; No active uptake by OATP1B1/3 expressed in HEK cells Ctrough concentrations increased by 40-49% when co-administered with cyclosporine and atazanavir CYP3A4 Km2 = 71 µM; Vmax2 = 0.004 nmol/min/pmol; Km1 = 7.1 µM; Vmax1 = 0.0001 nmol/min/pmol; AUC unchanged when with ketoconazole; AUC decreased 30% when with carbamazepine CYP2C8 Km = 79.1 µM; Vmax = 0.001 nmol/min/pmol; Unlikely P-gp, BCRP Contradictory: Ombitasvir was not a substrate of P-gp or BCRP mediated efflux in vitro, but mice lacking these transporters had increased exposure levels AUC unchanged when with cyclosporine; Cmax decreased by 23% when with atazanavir CYP2C8 CYP2C8 inhibitor quercetin inhibited in vitro metabolism in human liver microsomes by 60% Confirmed (AUC increased 1025% by gemfibrozil) CYP3A4 CYP3A inhibitor ketoconazole inhibited in vitro metabolism in human liver microsomes by 30% Confirmed (AUC increased 42% by ketoconazole; decreased 70% by carbamazepine P-gp Inhibited by LY335979 and cyclosporin A in vitro Confirmed C (AUC decreased 21% by OATP1B1 inhibitor atazanavir and 30% by inhibitor cyclosporin) BCRP Inhibited by BCRP inhibitor K0143 M1 BCRP Inhibited by BCRP inhibitor administered administered administered administered administered administered
auspar-paritaprevir-ritonavir-ombitasvir-dasabuvir-sodium-salt-170324.docx