title: Effects of the cholesteryl ester transfer protein inhibitor evacetrapib on lipoproteins, apolipoproteins and 24-h ambulatory blood pressure in healthy adults.
abstract: OBJECTIVE
  We investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of evacetrapib.
  
  
  METHODS
  Healthy volunteers received multiple daily doses of evacetrapib (10-600 mg) administered for up to 15 days in a placebo-controlled study.
  
  
  RESULTS
  Mean peak plasma concentrations of evacetrapib occurred at 4-6 h and terminal half-life ranged 24-44 h. Steady state was achieved at approximately 10 days; all subjects had undetectable levels of evacetrapib 3 weeks after their last dose. The trough inhibition of cholesteryl ester transfer protein (CETP) activity was 65 and 84% at 100 and 300 mg, respectively. At the highest dose (600 mg), evacetrapib significantly inhibited CETP activity (91%), increased HDL-C (87%) and apo AI (42%), and decreased LDL-C (29%) and apo B (26%) relative to placebo. For the highest dose tested, levels of evacetrapib, CETP activity, CETP mass, HDL-C and LDL-C returned to levels at or near baseline after a 2-week washout period. Evacetrapib at the highest dose tested did not produce any significant effect on 24-h ambulatory systolic or diastolic blood pressure.
  
  
  CONCLUSIONS
  Multiple doses of evacetrapib potently inhibited CETP activity, leading to substantial elevations in HDL-C and lowering of LDL-C. Evacetrapib was devoid of clinically relevant effects on blood pressure and mineralocorticoid levels.
authors: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors: Jeffrey G
authors: JG
authors: Suico
authors: Ming-Dauh
authors: MD
authors: Wang
authors: Stuart
authors: S
authors: Friedrich
authors: Ellen A
authors: EA
authors: Cannady
authors: Christopher S
authors: CS
authors: Konkoy
authors: Giacomo
authors: G
authors: Ruotolo
authors: Kathryn A
authors: KA
authors: Krueger
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000097:blood*; D001055:Apolipoproteins B / Q000097:blood*; D001569:Benzodiazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D001569:Benzodiazepines; C568301:evacetrapib
keywords: cholesteryl ester transfer protein; evacetrapib; high-density lipoprotein; pharmacodynamic; pharmacokinetic