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DDMODEL00000117: Friedrich_2014_LDL_evacetrapib

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Population PD Emax-model to analyze the relationship between evacetrapib AUC and percent change in HDL over time.
PharmML (0.6.1)
  • The pharmacokinetics and pharmacokinetic/pharmacodynamic relationships of evacetrapib administered as monotherapy or in combination with statins.
  • Friedrich S, Kastelein JJ, James D, Waterhouse T, Nissen SE, Nicholls SJ, Krueger KA
  • CPT: pharmacometrics & systems pharmacology, 1/2014, Volume 3, pages: e94
  • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Cleveland Clinic Coordinating Center for Clinical Research, Cleveland Clinic, Cleveland
  • 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.
Paolo Magni
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  • Model owner: Paolo Magni
  • Submitted: Dec 12, 2015 9:44:23 AM
  • Last Modified: Oct 13, 2016 6:16:34 PM
Revisions
  • Version: 9 public model Download this version
    • Submitted on: Oct 13, 2016 6:16:34 PM
    • Submitted by: Paolo Magni
    • With comment: Edited model metadata online.
  • Version: 7 public model Download this version
    • Submitted on: Jul 16, 2016 5:24:27 PM
    • Submitted by: Paolo Magni
    • With comment: Edited model metadata online.
  • Version: 5 public model Download this version
    • Submitted on: Jul 16, 2016 5:20:37 PM
    • Submitted by: Paolo Magni
    • With comment: Updated model annotations.
  • Version: 2 public model Download this version
    • Submitted on: Dec 12, 2015 9:44:23 AM
    • Submitted by: Paolo Magni
    • With comment: Edited model metadata online.
 
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