increased ribavirin bioavailability associated with telaprevir use in hepatitis c patients treated with pegylated interferon/ribavirin/telaprevir triple therapy

Anemia is more frequent in patients receiving telaprevir with pegylated interferon/ribavirin (pegifn/rbv) than in those receiving pegifn/rbv alone. the objective was to measure the impact of telaprevir on rbv bioavailability and to assess the concomitant renal function. thirtyseven hepatitis c virus (hcv) patients nonresponders to a previous course of pegifn/rbv therapy and retreated with triple therapy combining pegifn/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 rbvtelaprevir 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 firstgeneration hcv protease inhibitorbased therapy.