title: Absence of clinically relevant drug-drug interaction between odanacatib and digoxin after concomitant administration.
abstract: OBJECTIVE
  This study was conducted in order to assess the effect of multiple doses of odanacatib, a cathepsin (Cat)-K inhibitor, on the pharmacokinetics of digoxin.
  
  
  METHODS
  Twelve healthy male and female subjects received 0.5 mg digoxin and 50 mg odanacatib.
  
  
  METHODS
  This open label study was conducted to determine the effect of odanacatib on the plasma pharmacokinetics of immunoreactive digoxin. Subjects received a single oral dose of 0.5 mg digoxin followed by a 10-day washout, followed by 3 once-weekly oral doses of 50 mg odanacatib and co-administration with 0.5 mg digoxin with the last odanacatib dose. A linear mixed-effect model was used to analyze AUC0-120h. Safety and tolerability were assessed.
  
  
  RESULTS
  The estimated geometric-mean-ratio (90% confidence interval) for AUC0-120h was 0.95 (0.89, 1.01), which was within (0.80, 1.25) determined to demonstrate a lack of interaction. There were no serious AEs, discontinuations due to AEs, or clinically significant abnormalities in ECG or vital sign measurements.
  
  
  CONCLUSIONS
  This study demonstrated that 50 mg odanacatib did not lead to clinically important effects on the pharmacokinetics of 0.5 mg digoxin.
authors.affiliation: Merck Sharp & Dohme, Whitehouse Station, NJ, USA. aubrey_stoch@merck.com
authors.forename: S Aubrey
authors.initials: SA
authors.lastname: Stoch
authors.forename: Rose
authors.initials: R
authors.lastname: Witter
authors.forename: David
authors.initials: D
authors.lastname: Hreniuk
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Liu
authors.forename: Stefan
authors.initials: S
authors.lastname: Zajic
authors.forename: Anish
authors.initials: A
authors.lastname: Mehta
authors.forename: Christine
authors.initials: C
authors.lastname: Brandquist
authors.forename: Cynthia
authors.initials: C
authors.lastname: Dempsey
authors.forename: Bruce
authors.initials: B
authors.lastname: Degroot
authors.forename: Daria
authors.initials: D
authors.lastname: Stypinski
authors.forename: Andrew
authors.initials: A
authors.lastname: Denker
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
mesh_terms: D000328:Adult; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004077:Digoxin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D001713:Biphenyl Compounds; D004077:Digoxin; C527128:odanacatib