Increased Ribavirin Bioavailability Associated With Telaprevir Use in Hepatitis C Patients Treated With PEGylated -Interferon/Ribavirin/Telaprevir Triple Therapy.

Abstract

BACKGROUND:

Anemia is more frequent in patients receiving telaprevir with PEGylated interferon/ribavirin (PEG-IFN/RBV) than in those receiving PEG-IFN/RBV alone.

OBJECTIVES:

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

MATERIALS AND 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.

• Authors: Pierre Pradat, Victor Virlogeux, Marianne Maynard, Mathilde Leclercq, Giorgiana Hatu, Majid Amiri, Fanny Lebosse, Patrick Miailhes, Fabien Zoulim, Marie-Claude Gagnieu, François Bailly
• Journal: Hepatitis monthly (Hepat Mon) Vol. 15 Issue 9 Pg. e28879 (Sep 2015) ISSN: 1735-143X [Print] Netherlands
• PMID: 26500683 (Publication Type: Journal Article)