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

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 AUC(0-last) and AUC(0-∞) 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 C(max) were 1.23 (1.14, 1.32). Median T(max) and mean apparent terminal t(½) 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.

• Authors: Rajesh Krishna, Daria Stypinski, Melissa Ali, Amit Garg, Isaias Noel Gendrano 3rd, Andrea Maes, Bruce DeGroot, Yang Liu, Susie Li, Sandra M Connolly, John A Wagner, S Aubrey Stoch
• Journal: Biopharmaceutics & drug disposition (Biopharm Drug Dispos) Vol. 32 Issue 9 Pg. 525-9 (Dec 2011) ISSN: 1099-081X [Electronic] England
• PMID: 22031172 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 John Wiley & Sons, Ltd.

Chemical References

• Cardiotonic Agents
• Cholesterol Ester Transfer Proteins
• Drug Combinations
• Oxazolidinones
• Digoxin
• anacetrapib

Topics

• Adolescent
• Adult
• Area Under Curve
• Cardiotonic Agents (administration & dosage, blood, pharmacokinetics)
• Cholesterol Ester Transfer Proteins (antagonists & inhibitors)
• Digoxin (administration & dosage, blood, pharmacokinetics)
• Drug Combinations
• Female
• Half-Life
• Humans
• Male
• Middle Aged
• Oxazolidinones (administration & dosage)
• Young Adult