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

作者：Stoch S Aubrey^*; Witter Rose; Hreniuk David; Liu Chengcheng; Zajic Stefan; Mehta Anish; Brandquist Christine; Dempsey Cynthia; DeGroot Bruce; Stypinski Daria; Denker Andrew; Wagner John A

来源：International Journal of Clinical Pharmacology and Therapeutics, 2013, 51(8): 688-692.

DOI：10.5414/CP201864

• odanacatib
• digoxin
• P-glycoprotein

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 AUC(0-120h). Safety and tolerability were assessed. Results: The estimated geometric-mean-ratio (90% confidence interval) for AUC(0-120h) 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.

• 出版日期2013-8