Author/Authors :
Pradat، Pierre نويسنده Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France , , Virlogeux، Victor نويسنده Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France , , Maynard، Marianne نويسنده Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France , , Leclercq، Mathilde نويسنده Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France , , Hatu، Giorgiana نويسنده Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France , , Amiri، Majid نويسنده Hospices Civils de Lyon, Croix-Rousse Hospital, Department of Hepatology, Lyon, France Amiri, Majid , Lebosse، Fanny نويسنده Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France , , Miailhes، Patrick نويسنده Department of Infectious Diseases and Tropical Medicine, Hospices Civils de Lyon, Lyon, France , , Zoulim، Fabien نويسنده Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France , , Gagnieu، Marie-Claude نويسنده Department of Pharmacology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France , , Bailly، François نويسنده Department of Hepatology, Croix-Rousse Hospital, Hospices Civils of Lyon, Lyon, France ,
Abstract :
Anemia is more frequent in patients receiving telaprevir with PEGylated interferon/ribavirin (PEG-IFN/RBV) than in those receiving PEG-IFN/RBV alone. The objective was to measure the impact of telaprevir on RBV bioavailability and to assess the concomitant renal function. 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). 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). 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.
