Absence of clinically relevant drug-drug interaction between odanacatib and digoxin after concomitant administration

Int J Clin Pharmacol Ther. 2013 Aug;51(8):688-92. doi: 10.5414/CP201864.

Abstract

Objectives: 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.

Materials: 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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biphenyl Compounds / administration & dosage
  • Biphenyl Compounds / adverse effects
  • Biphenyl Compounds / pharmacology*
  • Digoxin / administration & dosage
  • Digoxin / adverse effects
  • Digoxin / pharmacokinetics*
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Middle Aged

Substances

  • Biphenyl Compounds
  • Digoxin
  • odanacatib