title: Pharmacodynamic effects of prasugrel dosing regimens in patients on maintenance prasugrel therapy: results of a prospective randomized study.
abstract: OBJECTIVE
  The purpose of this study is to assess the pharmacodynamic effects of different prasugrel dosing regimens in patients on maintenance prasugrel therapy.
  
  
  BACKGROUND
  There are a growing number of patients on chronic prasugrel therapy regimens, leading to questions about the dosing regimen of prasugrel to administer if percutaneous coronary intervention is required.
  
  
  METHODS
  This is a prospective pharmacodynamic study in patients (n = 64) receiving maintenance prasugrel therapy who were randomly allocated to a 10 mg, 30 mg, or 60 mg dose of prasugrel. Pharmacodynamic assessments using multiple assays were conducted at 3 timepoints (baseline and 1 h and 4 h after dosing).
  
  
  RESULTS
  Intragroup comparisons showed that a 60 mg dose reduced the platelet reactivity index (PRI) after 1 h (p = 0.004) and 4 h (p < 0.001, primary endpoint; p = 0.002 between 1 h and 4 h). A 30 mg dose also reduced PRI levels at 1 h (p = 0.006) and 4 h (p < 0.001; p = 0.044 between 1 h and 4 h). A 10 mg dose was associated with modest pharmacodynamic effects. Intragroup comparisons showed similar findings with VerifyNow-P2Y12 and light transmission aggregometry. Intergroup comparisons showed that a 60 mg dose achieved lower PRI levels than 30 mg at 4 h (p = 0.05), and a numerical trend toward better pharmacodynamic effects at 1 h (p = 0.171). Intergroup comparisons were similar with VerifyNow-P2Y12, but not light transmission aggregometry.
  
  
  CONCLUSIONS
  For patients on maintenance prasugrel therapy, a 60 mg dosing strategy is associated with faster and higher platelet inhibition compared with lower doses, as assessed by P2Y(12) specific assays. (Impact of Prasugrel Re-load on Platelet Aggregation in Patients on Chronic Prasugrel Therapy; NCT01201772).
authors.affiliation: University of Florida College of Medicine, Jacksonville, Jacksonville, Florida 32209, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Tello-Montoliu
authors.forename: Salvatore D
authors.initials: SD
authors.lastname: Tomasello
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ferreiro
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ueno
authors.forename: Naveen
authors.initials: N
authors.lastname: Seecheran
authors.forename: Bhaloo
authors.initials: B
authors.lastname: Desai
authors.forename: Murali
authors.initials: M
authors.lastname: Kodali
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Charlton
authors.forename: Lyndon C
authors.initials: LC
authors.lastname: Box
authors.forename: Martin M
authors.initials: MM
authors.lastname: Zenni
authors.forename: Luis A
authors.initials: LA
authors.lastname: Guzman
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005006:Ethnicity; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D000068799:Prasugrel Hydrochloride; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D005343:Fibrinolytic Agents; C548576:P2RY12 protein, human; D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride