title: Pharmacokinetic and pharmacodynamic effects of elinogrel: results of the platelet function substudy from the intravenous and oral administration of elinogrel to evaluate tolerability and efficacy in nonurgent percutaneous coronary intervention patients (INNOVATE-PCI) trial.
abstract: BACKGROUND
  Elinogrel is the only selective, competitive and reversible platelet P2Y(12) inhibitor available in both intravenous (IV) and oral formulations.
  
  
  RESULTS
  This substudy of the Intravenous and Oral Administration of Elinogrel to Evaluate Tolerability and Efficacy in Nonurgent Percutaneous Coronary Intervention patients (INNOVATE-PCI) trial evaluated the pharmacokinetic and pharmacodynamic effects of two dosing regimens of IV followed by oral elinogrel (120 mg IV plus 100 mg oral twice daily; 120 mg IV plus 150 mg oral twice daily) versus standard clopidogrel therapy (300-600 mg oral loading dose plus 75 mg oral maintenance dose) in 56 patients undergoing nonurgent PCI. At time of randomization, 71.4% (40/56) of patients were using maintenance clopidogrel therapy. In the acute phase, an IV bolus of elinogrel achieved more rapid and potent antiplatelet effects compared with clopidogrel, which were sustained during the transition from the IV to the oral formulation in the first 24 hours of the peri-PCI period. During chronic therapy, elinogrel achieved similar levels of platelet reactivity compared with clopidogrel before the next oral dose and, although platelet reactivity was lower with elinogrel up to 6 hours after daily oral maintenance dosing, these differences were not statistically significant. These pharmacodynamic effects matched the pharmacokinetic profile of elinogrel. There were no differences in pharmacodynamic and pharmacokinetic effects between the two elinogrel dosing regimens.
  
  
  CONCLUSIONS
  Compared with clopidogrel, the combination of IV and oral elinogrel achieves more rapid and enhanced antiplatelet effects that were sustained through the transition to oral elinogrel in the peri-PCI period, but these were not significant during chronic dosing in this pilot investigation.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751231.
authors.affiliation: University of Florida-Shands Jacksonville, Jacksonville, FL 32209, USA. dominick.angiolillo@jax.ufl.edu
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Robert C
authors.initials: RC
authors.lastname: Welsh
authors.forename: Dietmar
authors.initials: D
authors.lastname: Trenk
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Conley
authors.forename: Matthew W
authors.initials: MW
authors.lastname: McClure
authors.forename: Gillian
authors.initials: G
authors.lastname: Stephens
authors.forename: Janusz
authors.initials: J
authors.lastname: Kochman
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Jennings
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Jarosław
authors.initials: J
authors.lastname: Wójcik
authors.forename: Marek
authors.initials: M
authors.lastname: Dabrowski
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Saucedo
authors.forename: Juergen
authors.initials: J
authors.lastname: Stumpf
authors.forename: Michael
authors.initials: M
authors.lastname: Buerke
authors.forename: Samuel
authors.initials: S
authors.lastname: Broderick
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Rao
mesh_terms: D000284:Administration, Oral; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000401:mortality; D002170:Canada; D000077144:Clopidogrel; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010979:Platelet Function Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D052999:Quinazolinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014481:United States
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D052999:Quinazolinones; D058925:Receptors, Purinergic P2Y12; D013449:Sulfonamides; C549473:elinogrel; D000077144:Clopidogrel; D013988:Ticlopidine