Evacetrapib
Population PK/PD model finds evacetrapib exposure predicts up to a 177% HDL-C increase and 44.1% LDL-C decrease (CPT Pharmacometrics Syst Pharmacol 2014)
Original title: The pharmacokinetics and pharmacokinetic/pharmacodynamic relationships of evacetrapib administered as monotherapy or in combination with statins
Researchers analyzed evacetrapib concentration data alongside HDL-C and LDL-C data from a 12-week study of dyslipidemic patients treated with evacetrapib alone or combined with atorvastatin, simvastatin, or rosuvastatin. Evacetrapib pharmacokinetics were characterized using a two-compartment model with first-order absorption, with exposure increasing in a less than dose-proportional manner similar to other CETP inhibitors, and no patient factors had a clinically relevant impact on its pharmacokinetics. Emax models relating evacetrapib exposure to lipid response estimated a theoretical maximal mean HDL-C increase of 177% and LDL-C decrease of 44.1% relative to baseline, with HDL-C change negatively correlated with baseline HDL-C. A pharmacologically independent LDL-C reduction was observed when evacetrapib was coadministered with statins.
Original abstract
Evacetrapib is a novel cholesteryl ester transfer protein (CETP) inhibitor currently being evaluated in a late-stage cardiovascular outcome trial. Using population-based models, we analyzed evacetrapib concentration data along with high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) data from a 12-week study in dyslipidemic patients treated with evacetrapib alone or in combination with atorvastatin, simvastatin, or rosuvastatin. Evacetrapib pharmacokinetics were characterized using a two-compartment model with first-order absorption. Evacetrapib exposure increased in a less than dose-proportional manner, similar to other CETP inhibitors. No patient factors had a clinically relevant impact on evacetrapib pharmacokinetics. The relationships between evacetrapib exposure and HDL-C and LDL-C were characterized using Emax models. The theoretical maximal mean HDL-C increase and LDL-C decrease relative to baseline were 177 and 44.1%, respectively. HDL-C change from baseline was found to be negatively correlated with baseline HDL-C. A pharmacologically independent LDL-C reduction was found when evacetrapib was coadministered with statins.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e94; doi:10.1038/psp.2013.70; published online 22 January 2014.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.