Lack of an effect of anacetrapib on the pharmacokinetics of digoxin in healthy subjects

• Published in: Biopharmaceutics & drug disposition Vol. 32; no. 9; pp. 525 - 529
• Main Authors: Krishna, Rajesh, Stypinski, Daria, Ali, Melissa, Garg, Amit, Gendrano III, Isaias Noel, Maes, Andrea, DeGroot, Bruce, Liu, Yang, Li, Susie, Connolly, Sandra M., Wagner, John A., Stoch, S. Aubrey
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.12.2011
• Subjects: Adolescent; Adult; anacetrapib; Area Under Curve; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - blood; Cardiotonic Agents - pharmacokinetics; Cholesterol Ester Transfer Proteins - antagonists & inhibitors; co-administration; digoxin; Digoxin - administration & dosage; Digoxin - blood; Digoxin - pharmacokinetics; Drug Combinations; Female; Half-Life; Humans; Male; Middle Aged; Oxazolidinones - administration & dosage; Young Adult
• ISSN: 0142-2782; 1099-081X; 1099-081X
• DOI: 10.1002/bdd.776

ABSTRACT Anacetrapib is currently being developed for the oral treatment of dyslipidemia. A clinical study was conducted in healthy subjects to assess the potential for an interaction with orally administered digoxin. Anacetrapib was generally well tolerated when co‐administered with digoxin in the healthy subjects in this study. The geometric mean ratios (GMR) for (digoxin + anacetrapib/digoxin alone) and 90% confidence intervals (CIs) for digoxin AUC0‐last and AUC0‐∞ were 1.05 (0.96, 1.15) and 1.07 (0.98, 1.17), respectively, both being contained in the accepted interval of bioequivalence (0.80, 1.25), the primary hypothesis of the study. The GMR (digoxin + anacetrapib /digoxin alone) and 90% CIs for digoxin Cmax were 1.23 (1.14, 1.32). Median Tmax and mean apparent terminal t½ of digoxin were comparable between the two treatments. The single‐dose pharmacokinetics of orally administered digoxin were not meaningfully affected by multiple‐dose administration of anacetrapib, indicating that anacetrapib does not meaningfully inhibit P‐glycoprotein. Thus, no dosage adjustment for digoxin is necessary when co‐administered with anacetrapib. Copyright © 2011 John Wiley & Sons, Ltd.