title: Pharmacokinetics, safety, and tolerability of faldaprevir in patients with renal impairment.
abstract: Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor with negligible urinary excretion. We assessed the pharmacokinetics and safety of a single oral dose of faldaprevir (480 mg) in 32 HCV-negative subjects with renal impairment or normal renal function. Compared with subjects with normal renal function, the adjusted geometric mean ratios (90% confidence intervals in parentheses) for overall exposure area under the concentration-time curve from zero to infinity (AUC0-∞) were 113.6% (41.6 to 310.2%), 178.3% (85.2 to 373.0%), and 169.2% (73.2 to 391.2%) for subjects with mild, moderate, and severe renal impairment, respectively. Overall, 5/8 (63%) subjects with normal renal function and 20/24 (83%) subjects with renal impairment reported adverse events, with gastrointestinal events being the most common. No severe or serious adverse events or deaths were reported. These results suggest that moderate or severe renal impairment can result in a modest increase in faldaprevir exposure. The increase in exposure may be related to decrease in the activity of the liver uptake transporter OATP1B1 as a result of renal impairment. Given this relatively slight increase in exposure, a dose adjustment in HCV patients with renal impairment is not warranted. (This study has been registered at ClinicalTrials.gov under registration number NCT01957657.).
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA fenglei.huang@boehringer-ingelheim.com.
authors.forename: Fenglei
authors.initials: F
authors.lastname: Huang
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Moschetti
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lang
authors.affiliation: CRS Clinical Research Services Kiel GmbH, Kiel, Germany.
authors.forename: Atef
authors.initials: A
authors.lastname: Halabi
authors.affiliation: CRS Clinical Research Services Kiel GmbH, Kiel, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Petersen-Sylla
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.
authors.forename: Chan-Loi
authors.initials: CL
authors.lastname: Yong
authors.affiliation: Boehringer Ingelheim Ltd/Ltée, Burlington, ON, Canada.
authors.forename: Mabrouk
authors.initials: M
authors.lastname: Elgadi
mesh_terms: D000328:Adult; D000368:Aged; D000621:Aminoisobutyric Acids; D001682:Biological Availability; D005260:Female; D006207:Half-Life; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives; D011804:Quinolines; D051437:Renal Insufficiency / Q000503:physiopathology*; D013844:Thiazoles / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000621:Aminoisobutyric Acids; D009842:Oligopeptides; D011804:Quinolines; D013844:Thiazoles; C552340:faldaprevir; D011392:Proline; D007930:Leucine