title: Investigation of the effect of food and omeprazole on the relative bioavailability of a single oral dose of 240 mg faldaprevir, a selective inhibitor of HCV NS3/4 protease, in an open-label, randomized, three-way cross-over trial in healthy participants.
abstract: OBJECTIVE
  This study was conducted to investigate the effect of food and coadministration of omeprazole on the relative bioavailability (BA) of faldaprevir (FDV).
  
  
  METHODS
  Fifteen healthy participants participated in this open-label, randomized, three-way cross-over study. Faldaprevir was administered as a 240 mg single dose during fasting state, following intake of a high-fat breakfast, or following omeprazole 40 mg q.d. dosing for 5 days. PK samples were collected on the day of faldaprevir administration.
  
  
  RESULTS
  We found geometric mean (gMean) AUC0-∞ values for faldaprevir of 48 200, 37 900 and 36 000 ng h/ml under the fed, fasted and omeprazole coadministration conditions respectively. Similarly, gMean Cmax values for faldaprevir were 2600, 2030, 1920 ng/ml under the same respective conditions. The adjusted gMean ratio between the fed and fasted condition was approximately 120% for both AUC0-∞ and Cmax , while the ratio of omeprazole coadministration to fasted condition was approximately 94%. Faldaprevir was safe and well tolerated in the study.
  
  
  CONCLUSIONS
  Administration of a single dose of 240 mg faldaprevir after high-fat breakfast led to a modest, clinically irrelevant increase in faldaprevir exposure, while coadministration of omeprazole did not influence faldaprevir exposure.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gießmann
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lang
authors.affiliation: Boehringer Ingelheim Canada Ltd/Ltee, Burlington, ON, Canada.
authors.forename: Mabrouk
authors.initials: M
authors.lastname: Elgadi
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Fenglei
authors.identifier: http://orcid.org/0000-0002-0642-9401
authors.initials: F
authors.lastname: Huang
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D064368:Healthy Volunteers; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D009853:Omeprazole / Q000008:administration & dosage* / Q000009:adverse effects; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011804:Quinolines; D012307:Risk Factors; D013844:Thiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055815:Young Adult; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D007930:Leucine; D009842:Oligopeptides; D009853:Omeprazole; D011392:Proline; D011480:Protease Inhibitors; D054328:Proton Pump Inhibitors; D011804:Quinolines; D013844:Thiazoles; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C552340:faldaprevir
keywords: bioavailability; faldaprevir; food effect; omeprazole