Anacetrapib
Human phase 1 data confirm anacetrapib keeps accumulating in fat for a year while plasma levels plateau, explaining its long residence time (Clin Pharmacol Ther 2017)
Original title: Chronic Administration of Anacetrapib Is Associated With Accumulation in Adipose and Slow Elimination
Anacetrapib had shown residual pharmacological activity long after chronic dosing stopped in earlier clinical trials, and preclinical mouse data suggested white adipose tissue serves as a drug depot governing its long-term kinetics. This phase 1 study tested that hypothesis in humans and found plasma anacetrapib exposure correlated with the fat content of food taken with the dose. Plasma concentrations appeared to plateau faster than adipose concentrations, and anacetrapib continued accumulating in adipose tissue throughout the treatment period even after plasma levels had apparently plateaued, with only minimal decline in adipose levels up to 1 year after the last dose. The authors attribute this to the high lipophilicity of anacetrapib, which drives it to partition into adipose tissue, forming a drug reservoir that in turn extends its residence time in plasma, direct human confirmation of the mechanism behind the eventual regulatory withdrawal of anacetrapib.
Original abstract
Anacetrapib is a novel cholesteryl-ester transfer protein (CETP) inhibitor in late-stage clinical development, shown in preceding clinical trials to have residual pharmacological activity after prolonged washout after chronic dosing. Preclinical findings suggest that white adipose tissue is a potential depot and that accumulation into adipose tissue governs the long-term kinetics of anacetrapib in mice. A phase I study performed to test this hypothesis in humans revealed that plasma exposure was correlated with fat content in food administered with the drug. Plasma concentrations of anacetrapib seemed to reach plateau faster than adipose concentrations. Anacetrapib continued to accumulate in adipose during the treatment period despite apparent plateau in plasma with only minimal decline in adipose levels up to 1 year postdose. Because of its high lipophilicity, anacetrapib partitions into adipose tissue, this likely forms a drug reservoir that, in turn, contributes to the long residence time of the drug in plasma.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.