title: Lack of a clinically significant drug-drug interaction in healthy volunteers between the HCV protease inhibitor boceprevir and the proton pump inhibitor omeprazole.
abstract: OBJECTIVE
  Proton pump inhibitors (PPIs) can limit the solubility of concomitant drugs, which can lead to decreased absorption and exposure. Reduced efficacy can be a consequence and in the case of an antimicrobial agent this may contribute to development of resistance. Patients chronically infected with the hepatitis C virus can be treated with a boceprevir-containing regimen and it is relevant to know if interactions between PPIs and boceprevir exist. This study was designed to investigate the influence of a frequently used PPI, omeprazole, on the pharmacokinetics of boceprevir and vice versa.
  
  
  METHODS
  In this open-label, three-period, randomized, cross-over, Phase I study, healthy subjects were randomly assigned to 40 mg of omeprazole once daily for 5 days, 800 mg of boceprevir three times daily for 5 days and 40 mg of omeprazole once daily + 800 mg of boceprevir three times daily for 5 days, or the same treatment in a different order. Every treatment was followed by a wash-out period. At day 5 of every treatment pharmacokinetic blood sampling was performed for 8 h after medication intake. ClinicalTrials.gov: NCT01470690.
  
  
  RESULTS
  All 24 subjects (15 males) completed the study and no serious adverse events were reported. Geometric mean ratios (90% CI) of the area under the plasma concentration-time curve up to 8 h (AUC0-8) and maximum plasma concentration (Cmax) of boceprevir with omeprazole versus boceprevir alone were 0.92 (0.87-0.97) and 0.94 (0.86-1.02), respectively. For omeprazole these values were 1.06 (0.90-1.25) for AUC0-8 and 1.03 (0.85-1.26) for Cmax for the combination versus omeprazole alone.
  
  
  CONCLUSIONS
  Omeprazole did not have a clinically significant effect on boceprevir exposure, and boceprevir did not affect omeprazole exposure.
authors: Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. k.dekanter@akf.umcn.nl
authors: Clara T M M
authors: CT
authors: de Kanter
authors: Angela P H
authors: AP
authors: Colbers
authors: Maren I
authors: MI
authors: Blonk
authors: Corrien P W G M
authors: CP
authors: Verweij-van Wissen
authors: Bas J J W
authors: BJ
authors: Schouwenberg
authors: Joost P H
authors: JP
authors: Drenth
authors: David M
authors: DM
authors: Burger
mesh_terms: D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000009:adverse effects / Q000494:pharmacology*; D019540:Area Under Curve; D001711:Biotransformation; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006526:Hepatitis C / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000009:adverse effects / Q000493:pharmacokinetics*; D010349:Patient Compliance; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011480:Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000897:Anti-Ulcer Agents; D011480:Protease Inhibitors; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; D009853:Omeprazole
keywords: PPIs; drug interactions; hepatitis C virus; pharmacokinetics