title: Telaprevir impairs renal function and increases blood  ribavirin concentration during telaprevir/pegylated  interferon/ribavirin therapy for chronic hepatitis C.
abstract: We aimed to examine the relationship between renal dysfunction and anaemia that may develop during combination therapy involving pegylated interferon, ribavirin and telaprevir (PEG-IFN/RBV/TVR) for the treatment of chronic hepatitis C. Sixty-eight patients with genotype 1b high viral loads were treated with PEG-IFN/RBV/TVR. Peg-IFN and RBV doses were administered according to body weight. TVR was prescribed at 2250 mg/day for 44 patients and at 1500 mg/day for 24 patients who had low haemoglobin level (<12 g/dL). When anaemia had developed, the RBV dose was decreased. The serum TVR concentration at day 8 was measured, and the serum RBV concentration was measured serially. The estimated glomerular filtration rate (eGFR) was estimated to assess renal function. At week 1, serum TVR concentration was not correlated with a decrease in eGFR; however, the TVR dose, on a weight basis (mg/kg), and eGFR were correlated (r = 0.2691; P = 0.0265). Moreover, there was a negative correlation between eGFR and RBV serum concentration (r = −0.3694; P = 0.0025), and the serum RBV concentration and decrease in the haemoglobin were significantly correlated from week 1 to week 8. In triple therapy, the TVR dose per weight is correlated with a decline in renal function. Thus, the serum concentration of RBV increases, with a concomitant decrease in haemoglobin. It is important to adjust the doses of TVR and RBV to avoid excessive serum RBV levels and the development of severe anaemia, to achieve a good clinical effect.
authors.forename: T
authors.initials: T
authors.lastname: Karino
authors.forename: I
authors.initials: I
authors.lastname: Ozeki
authors.forename: S
authors.initials: S
authors.lastname: Hige
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Arakawa
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: Y
authors.initials: Y
authors.lastname: Kuwata
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Ohmura
authors.forename: J
authors.initials: J
authors.lastname: Toyota
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000998:Antiviral Agents / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D005919:Glomerular Filtration Rate; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects* / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000139:chemically induced*; D012254:Ribavirin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044967:Serum / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012254:Ribavirin; C486464:telaprevir