title: Effect of meal and antisecretory agents on the pharmacokinetics of danoprevir/ritonavir in healthy volunteers.
abstract: OBJECTIVE
  To evaluate the effect of a low- and high-fat meal and co-administration of ranitidine or omeprazole on the pharmacokinetics of ritonavir-boosted danoprevir (DNVr).
  
  
  METHODS
  In this randomised, open-label, cross-over study, healthy subjects received a single dose of DNVr. In group 1, DNVr was administered while fasting or with a low-fat or high-fat meal. In group 2, DNVr was administered alone or with ranitidine 150 mg (single dose) or omeprazole 40 mg (multiple doses).
  
  
  RESULTS
  Group 1 (n = 16): relative to fasting conditions, food slightly prolonged absorption but did not alter the extent of absorption. DNV area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞), maximum plasma concentration (C(max)), and plasma concentration 12 h after administration (C12h) geometric mean ratios (GMR%) (90% confidence interval (CI)) with a low-fat meal were 92.3 (80.2-106), 61.8 (51.0-74.9) and 95.2 (80.9-112), versus fasting conditions, and with a high-fat meal 99.5 (86.4-115), 58.9 (48.5-71.6) and 101 (86.0-119). Group 2 (n = 13): ranitidine or omeprazole had no clinically significant effect on DNV pharmacokinetics. DNV AUC0-∞, Cmax and C12h GMR% (90% CI) with ranitidine: 81.9 (68.3-98.1), 104 (86.9-123) and 87.5 (69.3-111), and with omeprazole: 83.0 (67.4-102), 92.7 (70.6-122) and 93.3 (65.6-133).
  
  
  CONCLUSIONS
  The absence of clinically relevant effects of food, ranitidine or omeprazole on DNVr pharmacokinetics suggests that DNVr can be administered without regard to meals and in combination with H2 antagonists or proton pump inhibitors.
authors.affiliation: Hoffmann-La Roche Inc, Nutley, NJ, USA.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Morcos
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Moreira
authors.forename: Mercidita T
authors.initials: MT
authors.lastname: Navarro
authors.forename: Núria
authors.initials: N
authors.lastname: Bech
authors.forename: Amanda
authors.initials: A
authors.lastname: Quatkemeyer
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Smith
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Brennan
mesh_terms: D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D003521:Cyclopropanes; D005260:Female; D018565:Food-Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D054833:Isoindoles; D007769:Lactams / Q000493:pharmacokinetics*; D047029:Lactams, Macrocyclic; D008297:Male; D062407:Meals; D009479:Neuropeptides / Q000494:pharmacology*; D009853:Omeprazole / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives; D011899:Ranitidine / Q000494:pharmacology; D019438:Ritonavir / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D003521:Cyclopropanes; D054833:Isoindoles; D007769:Lactams; D047029:Lactams, Macrocyclic; D009479:Neuropeptides; D013449:Sulfonamides; C049628:antisecretory factor; D011899:Ranitidine; C553752:danoprevir; D011392:Proline; D009853:Omeprazole; D019438:Ritonavir
keywords: food; omeprazole; pharmacokinetics; ranitidine; ritonavir-boosted danoprevir