title: Crushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Intervention: The CRUSH Study.
abstract: BACKGROUND
  Platelet inhibitory effects induced by oral P2Y12 receptor antagonists are delayed in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), which may be attributed to impaired absorption affecting drug pharmacokinetics (PK) and pharmacodynamics (PD). Crushing tablets has been suggested to lead to more favorable PK/PD profiles. To date, no studies have investigated the PK/PD effects of crushing prasugrel.
  
  
  OBJECTIVE
  This study sought to determine whether crushing prasugrel is associated with more favorable drug bioavailability and platelet inhibitory effects compared with whole tablets in STEMI patients undergoing PPCI.
  
  
  METHODS
  Our prospective, randomized, open-label study assessed STEMI patients undergoing PPCI (n = 52) who were treated with a prasugrel 60-mg loading dose (LD) either as whole or crushed tablets. PK/PD analyses were performed at 7 time points. PD effects were measured as P2Y12 reaction units and platelet reactivity index, and PK by plasma levels of prasugrel's active metabolite.
  
  
  RESULTS
  Compared with whole tablets, crushed prasugrel led to reduced P2Y12 reaction units by 30 min post-LD, which persisted at 1, 2 (164 vs. 95; least square mean difference = 68; 95% confidence interval: 10 to 126; primary endpoint), and 4 h post-LD. Significant differences were no longer present at 6 h post-LD. Parallel findings were shown with platelet reactivity index. Accordingly, high on-treatment platelet reactivity rates were reduced with crushed prasugrel. PK analyses showed a >3-fold faster absorption with crushed compared with whole prasugrel.
  
  
  CONCLUSIONS
  In STEMI patients undergoing PPCI, crushed prasugrel leads to faster drug absorption, and consequently, more prompt and potent antiplatelet effects compared with whole tablet ingestion. (Pharmacological Effects of Crushing Prasugrel in STEMI Patients; NCT02212028).
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rollini
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Francesco
authors.initials: F
authors.lastname: Franchi
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Jenny
authors.initials: J
authors.lastname: Hu
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Megha
authors.initials: M
authors.lastname: Kureti
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Niti
authors.initials: N
authors.lastname: Aggarwal
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Durairaj
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Yongwhi
authors.initials: Y
authors.lastname: Park
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Michael
authors.initials: M
authors.lastname: Seawell
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cox-Alomar
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Zenni
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Guzman
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Siva
authors.initials: S
authors.lastname: Suryadevara
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Patrick
authors.initials: P
authors.lastname: Antoun
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida. Electronic address: dominick.angiolillo@jax.ufl.edu.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011446:Prospective Studies; D058925:Receptors, Purinergic P2Y12 / Q000097:blood; D000072657:ST Elevation Myocardial Infarction / Q000628:therapy*; D013607:Tablets
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D013607:Tablets; D000068799:Prasugrel Hydrochloride
keywords: crushed tablet; pharmacodynamic; pharmacokinetic; platelets