Anacetrapib
Anacetrapib leaves simvastatin pharmacokinetics unchanged while adding incremental LDL-C lowering when combined (Br J Clin Pharmacol 2009)
Original title: Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects
Since anacetrapib is likely to be used alongside statins, this randomized, two-period, crossover study in 12 healthy subjects tested for a pharmacokinetic interaction with simvastatin. Subjects received simvastatin 40 mg alone or anacetrapib 150 mg co-administered with simvastatin 40 mg daily for 14 days each, separated by a washout period of at least 14 days. Both treatments were well tolerated, and simvastatin and simvastatin acid pharmacokinetics were similar with and without anacetrapib, with AUC0-24h geometric mean ratios of 1.36 (90% CI 1.17, 1.57) for simvastatin acid and 1.30 (90% CI 1.14, 1.47) for simvastatin, both within the prespecified comparability bounds of (0.50, 2.00). LDL-C fell by a mean of -36% (95% CI -27, -46) with simvastatin alone versus -54% (95% CI -44, -63) with anacetrapib co-administered, showing that anacetrapib does not meaningfully alter simvastatin pharmacokinetics while adding incremental LDL-C-lowering efficacy through CETP inhibition, with the combination well tolerated.
Original abstract
Aims: Anacetrapib is an orally active, potent inhibitor of cholesteryl ester transfer protein (CETP), which is in development for the treatment of dyslipidaemia. Because of the likely use of anacetrapib with hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, we aimed to evaluate the potential for a pharmacokinetic interaction with simvastatin.
Methods: A randomized, two-period, two-treatment, balanced, open-label, crossover study in 12 healthy subjects was performed. Subjects received simvastatin 40 mg alone or anacetrapib 150 mg co-administered with simvastatin 40 mg, once daily. Both treatments were administered following a low-fat breakfast for 14 days, separated by a wash-out period of at least 14 days. Safety and tolerability, simvastatin and simvastatin acid concentrations, and lipoproteins, were assessed.
Results: Both treatments were well tolerated. The pharmacokinetics of simvastatin and simvastatin acid were similar with and without anacetrapib administration {AUC(0-24 h) geometric mean ratio [90% confidence interval (CI)] for simvastatin acid and simvastatin were 1.36 [1.17, 1.57] and 1.30 [1.14, 1.47], respectively} based on the prespecified comparability bounds of (0.50, 2.00). Treatment with simvastatin alone led to a mean (95% CI) % reduction from baseline in low-density lipoprotein-cholesterol (LDL-C) of -36% (-27, -46) compared with a reduction of -54% (-44, -63) for anacetrapib co-administered with simvastatin.
Conclusions: There appears to be no clinically meaningful effect of anacetrapib on the pharmacokinetic parameters of simvastatin. When co-administered with simvastatin, anacetrapib appeared to exhibit incremental LDL-C-lowering efficacy, due to CETP inhibition. Co-administration of anacetrapib and simvastatin was well tolerated.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.