Effect of chronic hepatitis C on the activity of the membrane transporters P-gp and OATP1B1/BCRP on patients with different stages of hepatic fibrosis.

The activity of the membrane transporters OATP1B1 & BCRP (rosuvastatin) and P-gp (fexofenadine) was evaluated in patients with chronic hepatitis C virus (HCV) infection (n = 28), genotypes 1 and 3, investigated before the treatment with direct-acting antiviral agents (Phase 1) and up to 30 days after the assessment of the virologic response (Phase 2). Participants allocated in Groups 1 (n = 15; F0/F1 and F2, mild to moderate liver fibrosis) and 2 (n = 13; F3 and F4, advanced course of liver fibrosis/cirrhosis) received in both phases fexofenadine (10 mg) and rosuvastatin (2 mg). OATP1B1 & BCRP activity (rosuvastatin AUC 0-∞ ) was reduced in Groups 1 and 2, respectively, by 25% [ratio 0.75 (0.53-0.82), p < 0.01)] and 31% [ratio 0.69 (0.46-0.85), p < 0.05)] in Phase 1 compared to Phase 2. OATP1B1 & BCRP activity was reduced in Phases 1 and 2, respectively, by 49% [median ratio 1.51 (1.17-2.20), p < 0.05)] and 61% [ratio 1.39 (1.16-2.02), p < 0.01)] in Group 2 compared to Group 1. P-gp activity (fexofenadine AUC 0-∞ ) was also reduced in Phase 1 compared to Phase 2 [ratio Phase2/Phase1 0.79 (0.66-0.96 in Group 1 and 0.81 (0.69-0.96) in Group 2] as well as in Group 2 compared to Group 1 in both Phases [ratio Group2/Group1 1.47 (1.08-2.01) in Phase 1 and 1.51 (1.10-2.07 in Phase 2). Thus, the administration of OATP1B1 & BCRP and P-gp substrates with low therapeutic indexes should consider the evolution of the treatment and the stage of HCV infection.