title: Telaprevir drug monitoring during antiviral therapy of hepatitis C graft infection after liver transplantation.
abstract: OBJECTIVE
  Recurrence of hepatitis C virus (HCV) infection after orthotopical liver transplantation (OLT) is common and associated with reduced graft and patient survival. The protease inhibitor telaprevir may enhance virological response rates in patients after OLT in combination with pegylated interferon-alfa and ribavirin. Pharmacokinetic studies have shown significant drug-drug interactions between telaprevir and immunosuppression (IS), but telaprevir pharmacokinetics in OLT patients with IS are unknown. Aim of the present study was to analyse telaprevir plasma concentrations in patients with HCV genotype 1 infection after OLT in comparison to patients without OLT and IS.
  
  
  METHODS
  Five patients with HCV genotype 1 infection after OLT and 37 HCV genotype 1-infected patients patients without prior OLT were treated with telaprevir 2250 mg daily, ribavirin 1000/1200 mg daily and pegylated interferon-alfa-2a 180 μg once weekly (triple therapy). Telaprevir plasma concentrations were analysed by liquid chromatography-electrospray-ionization-tandem mass spectrometry. HCV RNA was assessed by automatized reverse-transcription polymerase chain-reaction.
  
  
  RESULTS
  Median (range) telaprevir plasma concentrations of TW 4, 8 and 12 were 3970 (1980-4430) ng/ml and 2520 (1870-8730) ng/ml in patients after OLT and ciclosporin- or tacrolimus-based IS, respectively, as compared to 2790 (1870-3140) in non-OLT patients (P = 0.3). In one patient with tacrolimus-based IS, telaprevir dose had to be adjusted to achieve virological response. Telaprevir plasma concentrations were steady at treatment weeks 4, 8 and 12 in patients with and without IS.
  
  
  CONCLUSIONS
  Telaprevir drug monitoring may be necessary in patients with tacrolimus-based IS in patients with HCV graft infection after OLT.
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, Frankfurt, 60590, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Farnik
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Wolf O
authors.initials: WO
authors.lastname: Bechstein
authors.forename: Bernd
authors.initials: B
authors.lastname: Kronenberger
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Sandra
authors.initials: S
authors.lastname: Labocha
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreiros
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Martin W
authors.initials: MW
authors.lastname: Welker
mesh_terms: D000998:Antiviral Agents / Q000097:blood* / Q000627:therapeutic use; D002853:Chromatography, Liquid; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D016898:Interferon-alpha / Q000627:therapeutic use; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods; D009842:Oligopeptides / Q000097:blood* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D016559:Tacrolimus / Q000627:therapeutic use*; D053719:Tandem Mass Spectrometry
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a; D016559:Tacrolimus
keywords: HCV; OLT; drug monitoring; telaprevir