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Anacetrapib

Anacetrapib does not meaningfully inhibit P-glycoprotein, leaving digoxin exposure essentially unchanged (Biopharm Drug Dispos 2011)

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

Biopharm Drug Dispos · · 5

Krishna R, Stypinski D, Ali M, Garg A, Gendrano IN, Maes A, DeGroot B, Liu Y, Li S, Connolly SM, Wagner JA, Stoch SA

To assess whether anacetrapib interacts with orally administered digoxin, a P-glycoprotein substrate with a narrow therapeutic window, this study co-administered the two drugs in healthy subjects. Anacetrapib was generally well tolerated with digoxin. The geometric mean ratios (digoxin plus anacetrapib versus digoxin alone) and 90% CIs for digoxin AUC0-last and AUC0-infinity were 1.05 (0.96, 1.15) and 1.07 (0.98, 1.17), both within the bioequivalence interval of (0.80, 1.25), supporting the primary study hypothesis; the ratio and 90% CI for digoxin Cmax was 1.23 (1.14, 1.32), and median Tmax and mean apparent terminal half-life of digoxin were comparable between treatments. These results show single-dose digoxin pharmacokinetics were not meaningfully altered by multiple-dose anacetrapib, indicating anacetrapib does not meaningfully inhibit P-glycoprotein and that no digoxin dosage adjustment is needed during co-administration.

Read the paper (DOI)PubMed

Original 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.

anacetrapibpharmacologysafety

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.