title: Pharmacokinetics of bound and unbound telaprevir in cirrhotic patients with moderate and severe hepatic impairment.
abstract: This study aimed to characterize the pharmacokinetic parameters of telaprevir (TVR) in patients with moderate and severe hepatic impairment, measure the unbound (pharmacologically active) plasma concentrations of TVR, and determine if any changes in TVR exposure were of clinical relevance. Ten patients with moderate (Child-Pugh B) hepatic impairment, 10 matched healthy control volunteers, and 4 nonmatched patients with severe (Child-Pugh C) hepatic impairment received 750 mg TVR every 8 hours for 6 days. Venous blood samples were collected at various times throughout the study. Single-dose and steady-state pharmacokinetics of total and unbound TVR were calculated. Safety and tolerability of TVR were also assessed. The mean maximum plasma concentration and area under the curve values of total and unbound TVR were lower in patients with moderate hepatic impairment compared with matched healthy controls following a single dose and at steady state but did not consistently meet statistical significance. This trend was also present when patients with severe hepatic impairment were compared with the nonmatched healthy controls. However, the safety profile of TVR in the patient and healthy volunteer groups was comparable with previously published data. These results indicate that reduced plasma concentrations of total and unbound TVR in patients with hepatic impairment are unlikely to be clinically relevant.
authors.affiliation: Janssen Research and Development, Beerse, Belgium.
authors.forename: Sivi
authors.initials: S
authors.lastname: Ouwerkerk-Mahadevan
authors.affiliation: CRS Clinical Research Services, Kiel, Germany.
authors.forename: Atef
authors.initials: A
authors.lastname: Halabi
authors.affiliation: PRA International, Prague, Czech Republic.|1st Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Cieslarová
authors.affiliation: Janssen Research and Development, Beerse, Belgium.
authors.forename: Indra
authors.initials: I
authors.lastname: Aerts
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: James
authors.initials: J
authors.lastname: Witek
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: Rodica
authors.initials: R
authors.lastname: Van Solingen-Ristea
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: Donghan
authors.initials: D
authors.lastname: Luo
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; C486464:telaprevir
keywords: hepatic function; hepatitis C; pharmacokinetics; single dose; steady state