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Lack of an effect of anacetrapib on the pharmacokinetics of digoxin in healthy subjects
Author(s) -
Krishna Rajesh,
Stypinski Daria,
Ali Melissa,
Garg Amit,
Gendrano Isaias Noel,
Maes Andrea,
DeGroot Bruce,
Liu Yang,
Li Susie,
Connolly Sandra M.,
Wagner John A.,
Stoch S. Aubrey
Publication year - 2011
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.776
Subject(s) - digoxin , pharmacokinetics , medicine , pharmacology , bioequivalence , heart failure
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. Copyright © 2011 John Wiley & Sons, Ltd.