title: Phase 0 study of the inhibition of cholesteryl ester transfer protein activity by JNJ-28545595 in plasma from normolipidemic and dyslipidemic humans.
abstract: OBJECTIVE
  To assess and validate the application of a non-radioactive assay for cholesteryl ester transfer protein (CETP) activity in clinical samples.
  
  
  METHODS
  In this Phase 0 study, CETP activity was measured following addition of the CETP inhibitor JNJ-28545595 to plasma samples from normolipidemic and three subgroups of dyslipidemic subjects with differing lipid profiles.
  
  
  RESULTS
  CETP activity was elevated in plasma samples from dyslipidemic subjects compared to normolipidemic subjects. Increased triglyceride levels correlated with decreased CETP inhibition. The assay was found to have good analytical precision and high throughput potential as required for clinical trial sample analysis.
  
  
  CONCLUSIONS
  The results demonstrate that pharmacological inhibition of CETP is affected by the dyslipidemic nature of plasma samples. In addition, since the optimal degree of CETP inhibition for maximal cardiovascular benefit in patients is not known, this assay may be used to help define optimal dosing of CETP inhibitors.
authors.affiliation: Cardiovascular and Metabolic Therapeutic Area.
authors.forename: Troy C
authors.initials: TC
authors.lastname: Sarich
authors.forename: Margery A
authors.initials: MA
authors.lastname: Connelly
authors.forename: Dorota B
authors.initials: DB
authors.lastname: Schranz
authors.forename: Atalanta
authors.initials: A
authors.lastname: Ghosh
authors.forename: Prasarn
authors.initials: P
authors.lastname: Manitpisitkul
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Leary
authors.forename: Paul
authors.initials: P
authors.lastname: Rothenberg
authors.forename: Keith T
authors.initials: KT
authors.lastname: Demarest
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Damiano
mesh_terms: D000328:Adult; D000368:Aged; D001681:Biological Assay / Q000379:methods*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000097:blood*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D008055:Lipids; D014280:Triglycerides