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

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. 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).