title: Pharmacokinetics of neratinib during coadministration with lansoprazole in healthy subjects.
abstract: To evaluate the effect of lansoprazole, a proton-pump inhibitor, on the absorption, pharmacokinetics, and safety of neratinib, a pan-HER tyrosine kinase inhibitor, in healthy subjects.
  
  
  
  This was an open-label, two-period, fixed-sequence study. Fifteen healthy adult subjects received a single oral dose of neratinib 240 mg (Period 1), followed by a washout period, then oral lansoprazole 30 mg once daily for 7 days and a single dose of neratinib 240 mg on Day 5 (Period 2). Pharmacokinetic sampling was performed for 72 h following each neratinib dose. Plasma neratinib concentration-time data were analysed using noncompartmental methods. Geometric mean ratios for AUC0-t, AUC0-inf, and peak plasma concentrations (Cmax) for neratinib plus lansoprazole vs. neratinib were used to assess the magnitude of the drug-drug interaction if the 90% confidence intervals were outside 80.00-125.00%.
  
  
  
  Neratinib geometric least-squares mean (LSM) Cmaxwas reduced from 84.5 ng ml-1with neratinib alone to 24.5 ng ml-1with neratinib plus lansoprazole. The extent of exposure to neratinib was also decreased: geometric LSM AUC0-twas 1478 ng ml-1h with neratinib vs. 426 ng ml-1h with neratinib plus lansoprazole, and geometric LSM AUC0-infwas 1557 ng ml-1h vs. 542 ng ml-1h, respectively. Mean t½was similar with both treatments (approximately 14 h). Geometric mean ratios 90% confidence intervals for AUC0-t, AUC0-infand Cmaxfell outside the prespecified equivalence range (80.0-125.0%). Treatment-emergent adverse events, all mild, were reported by five (33%) subjects.
  
  
  
  Coadministration of lansoprazole with neratinib reduced the rate and extent of neratinib exposure in healthy subjects.
authors.affiliation: Puma Biotechnology, Inc., Los Angeles, California, USA.
authors.forename: Kiana
authors.initials: K
authors.lastname: Keyvanjah
authors.affiliation: Puma Biotechnology, Inc., Los Angeles, California, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: DiPrimeo
authors.affiliation: Puma Biotechnology, Inc., Los Angeles, California, USA.
authors.forename: Ai
authors.initials: A
authors.lastname: Li
authors.affiliation: Data Management and Biometrics, Celerion, Lincoln, Nebraska, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Obaidi
authors.affiliation: Celerion, Tempe, Arizona, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Swearingen
authors.affiliation: Puma Biotechnology, Inc., Los Angeles, California, USA.
authors.forename: Alvin
authors.initials: A
authors.lastname: Wong
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D064747:Lansoprazole / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D011804:Quinolines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D047428:Protein Kinase Inhibitors; D054328:Proton Pump Inhibitors; D011804:Quinolines; D064747:Lansoprazole; C487932:neratinib
keywords: drug interaction; healthy volunteers; lansoprazole; neratinib; pharmacokinetics; safety