title: Pharmacodynamics and pharmacokinetics of the novel PAR-1 antagonist vorapaxar (formerly SCH 530348) in healthy subjects.
abstract: OBJECTIVE
  The aim of our study was to evaluate the pharmacology of vorapaxar (SCH 530348), an oral PAR-1 antagonist, in healthy volunteers.
  
  
  RESULTS
  In two randomized, placebo-controlled studies, subjects received either single ascending doses of vorapaxar (0.25, 1, 5, 10, 20, or 40 mg; n = 50), multiple ascending doses of vorapaxar (1, 3, or 5 mg/day for 28 days; n = 36), a loading dose (10 or 20 mg) followed by daily maintenance doses (1 mg) for 6 days (n = 12), or placebo. Single 20- and 40-mg doses of vorapaxar completely inhibited thrombin receptor activating peptide (TRAP)-induced platelet aggregation (>80% inhibition) at 1 h and sustained this level of inhibition for ≥72 h. Multiple doses yielded complete inhibition on Day 1 (5 mg/day) and Day 7 (1 and 3 mg/day). Adverse events were generally mild, transient, and unrelated to dose.
  
  
  CONCLUSIONS
  Vorapaxar provided rapid and sustained dose-related inhibition of platelet aggregation without affecting bleeding or clotting times.
authors.affiliation: Merck, Whitehouse Station, NJ, USA. teddy.kosoglou2@merck.com
authors.forename: Teddy
authors.initials: T
authors.lastname: Kosoglou
authors.forename: Larisa
authors.initials: L
authors.lastname: Reyderman
authors.forename: Renger G
authors.initials: RG
authors.lastname: Tiessen
authors.forename: André A
authors.initials: AA
authors.lastname: van Vliet
authors.forename: Robert R
authors.initials: RR
authors.lastname: Fales
authors.forename: Robert
authors.initials: R
authors.lastname: Keller
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: David L
authors.initials: DL
authors.lastname: Cutler
mesh_terms: D000293:Adolescent; D000328:Adult; D001760:Bleeding Time; D005260:Female; D006801:Humans; D007783:Lactones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar