Increased Ribavirin Bioavailability Associated With Telaprevir Use in Hepatitis C Patients Treated With PEGylated -Interferon/Ribavirin/Telaprevir Triple Therapy.
BACKGROUND
Anemia is more frequent in patients receiving telaprevir with PEGylated interferon/ribavirin (PEG-IFN/RBV) than in those receiving PEG-IFN/RBV alone.


OBJECTIVE
The objective was to measure the impact of telaprevir on RBV bioavailability and to assess the concomitant renal function.


METHODS
Thirty-seven hepatitis C virus (HCV) patients non-responders to a previous course of PEG-IFN/RBV therapy and re-treated with triple therapy combining PEG-IFN/RBV and telaprevir were analyzed. RBV bioavailability was measured before the triple therapy initiation, during telaprevir treatment at week (W) 4 and W8, and after telaprevir cessation (post W16). The renal function was assessed by estimating the glomerular filtration rate (eGFR).


RESULTS
At W4, RBV bioavailability, expressed as mg/L/daily dose/kg body weight, was significantly increased (median increase = 0.06 mg/L/dose/kg; P < 0.001). In parallel, the renal function was impaired with a mean eGFR decrease of -6.8 mL/minutes/1.73 m² (P = 0.109). Between W4 and W8, RBV bioavailability continued to increase (P < 0.001) but subsequently decreased slightly after telaprevir discontinuation with a concomitant restoration of the renal function (eGFR increase of 6.34 mL/minutes/1.73 m²).


CONCLUSIONS
Our results indicated a reversible increase in RBV bioavailability after telaprevir exposure, which might be linked to the impairment of the GFR. This also suggests a RBV-telaprevir pharmacological interaction, a possible source of severe anemia observed under triple therapy. These results suggest that RBV pharmacological monitoring may be clinically relevant, especially in the context of first-generation HCV protease inhibitor-based therapy.
Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France ; National Institute of Health and Medical Research (INSERM) U1052, Lyon, France ; Claude Bernard Lyon 1 University, Lyon, France.
Pierre
P
Pradat
Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France ; Ecole Normale Superieure, Lyon, France.
Victor
V
Virlogeux
Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France ; National Institute of Health and Medical Research (INSERM) U1052, Lyon, France ; Claude Bernard Lyon 1 University, Lyon, France.
Marianne
M
Maynard
Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France.
Mathilde
M
Leclercq
Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France ; University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Giorgiana
G
Hatu
Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France.
Majid
M
Amiri
Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France ; National Institute of Health and Medical Research (INSERM) U1052, Lyon, France ; Claude Bernard Lyon 1 University, Lyon, France.
Fanny
F
Lebosse
Department of Infectious Diseases and Tropical Medicine, Hospices Civils de Lyon, Lyon, France.
Patrick
P
Miailhes
Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France ; National Institute of Health and Medical Research (INSERM) U1052, Lyon, France ; Claude Bernard Lyon 1 University, Lyon, France ; Institut Universitaire of France, Paris, France.
Fabien
F
Zoulim
Department of Pharmacology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
Marie-Claude
MC
Gagnieu
Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France ; National Institute of Health and Medical Research (INSERM) U1052, Lyon, France ; Claude Bernard Lyon 1 University, Lyon, France.
François
F
Bailly
Anemia; Antiviral Agents; Glomerular Filtration Rate; Hepatitis C; Ribavirin; Telaprevir