Anacetrapib
Anacetrapib has no clinically meaningful interaction with warfarin, sparing patients a dosage adjustment (Br J Clin Pharmacol 2012)
Original title: Lack of a meaningful effect of anacetrapib on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects
Because warfarin, an anticoagulant with a narrow therapeutic index, is likely to be commonly prescribed alongside anacetrapib in dyslipidaemia patients, this randomized, open-label, two-period fixed-sequence study in 12 healthy men tested for a drug interaction. Subjects received a single 30 mg warfarin dose alone, then after washout received warfarin 30 mg on day 1 of a 100 mg daily anacetrapib regimen spanning day -14 through day 7. Geometric mean ratios and 90% CIs for warfarin AUC0-infinity with anacetrapib versus alone were 0.94 (0.90, 0.97) for R(+)-warfarin and 0.93 (0.87, 0.98) for S(-)-warfarin, and for Cmax were 1.01 (0.97, 1.05) for both enantiomers, all within the no-effect bounds of (0.80, 1.25); the INR AUC0-168h ratio was 0.93 (0.89, 0.96). These results show anacetrapib does not meaningfully affect warfarin pharmacokinetics or pharmacodynamics, indicating no clinically relevant effect on CYP2C9 and no need for warfarin dosage adjustment during co-administration.
Original abstract
What Is Already Known About This Subject: • Inhibition of cholesteryl ester transfer protein (CETP) is a potential new mechanism for the treatment of dyslipidaemia. Anacetrapib is a novel CETP inhibitor in development. Warfarin is a commonly prescribed anticoagulant that has a narrow therapeutic index. A drug interaction study for warfarin with a novel CETP inhibitor is expected to be helpful in defining dosing regimens. WHAT THIS STUDY: ADDS • This is the first study to show that there is no clinically meaningful pharmacokinetic interaction between anacetrapib and warfarin. The single dose pharmacokinetics and pharmacodynamics of orally administered warfarin were not meaningfully affected by multiple dose administration of anacetrapib, indicating that anacetrapib does not affect CYP 2C9 clinically. Thus, no dosage adjustment for warfarin is necessary when co-administered with anacetrapib.
Aim: Anacetrapib is currently being developed for the treatment of dyslipidaemia. Since warfarin, an anticoagulant with a narrow therapeutic index, is expected to be commonly prescribed in this population, a drug interaction study was conducted.
Methods: In a randomized, open-label, two-period fixed-sequence design, 12 healthy male subjects received two different treatments (treatment A followed by treatment B). In treatment A, a single oral dose of 30 mg warfarin (3 × 10 mg Coumadin(TM) ) was administered on day 1. After a washout interval, subjects began treatment B, where they were given daily 100 mg doses of anacetrapib (1 × 100 mg) beginning on day -14 and continuing through day 7, with concomitant administration of 30 mg warfarin (3 × 10 mg) on day 1. All anacetrapib and warfarin doses were administered with a standard low fat breakfast. After warfarin concentrations and prothrombin time were measured, standard pharmacokinetic, pharmacodynamic and statistical (linear mixed effects model) analyses were applied.
Results: Anacetrapib was generally well tolerated when co-administered with warfarin in the healthy males in this study. The geometric mean ratios (GMRs) for warfarin + anacetrapib : warfarin alone and 90% confidence interval (CIs) for warfarin AUC((0-∞)) were 0.94 (0.90, 0.97) for the R(+) warfarin enantiomer and 0.93 (0.87, 0.98) for the S(-) warfarin enantiomer, both being contained in the interval (0.80, 1.25), supporting the primary hypothesis of the study. The GMRs warfarin + anacetrapib : warfarin alone and 90% CIs for the statistical comparison of warfarin C(max) were 1.01 (0.97, 1.05) for both the R(+) warfarin and the S(-) warfarin enantiomers, and were also contained in the interval (0.80, 1.25). The GMR (warfarin + anacetrapib : warfarin alone) and 90% CI for the statistical comparison of INR AUC((0-168 h)) was 0.93 (0.89, 0.96).
Conclusion: The single dose pharmacokinetics and pharmacodynamics of orally administered warfarin were not meaningfully affected by multiple dose administration of anacetrapib, indicating that anacetrapib does not affect CYP 2C9 clinically. Thus, no dosage adjustment for warfarin is necessary when co-administered with anacetrapib.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.