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

Circ Cardiovasc Interv. 2012 Jun;5(3):347-56. doi: 10.1161/CIRCINTERVENTIONS.111.965608. Epub 2012 May 22.

Abstract

Background: Elinogrel is the only selective, competitive and reversible platelet P2Y(12) inhibitor available in both intravenous (IV) and oral formulations.

Methods and 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.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751231.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Angioplasty, Balloon, Coronary* / adverse effects
  • Angioplasty, Balloon, Coronary* / mortality
  • Canada
  • Clopidogrel
  • Double-Blind Method
  • Drug Administration Schedule
  • Europe
  • Female
  • Heart Diseases / blood
  • Heart Diseases / mortality
  • Heart Diseases / therapy*
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Models, Statistical
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Platelet Function Tests
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / pharmacokinetics*
  • Quinazolinones / administration & dosage
  • Quinazolinones / adverse effects
  • Quinazolinones / pharmacokinetics*
  • Receptors, Purinergic P2Y12 / drug effects
  • Receptors, Purinergic P2Y12 / metabolism
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Sulfonamides / pharmacokinetics*
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics
  • Treatment Outcome
  • United States

Substances

  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Quinazolinones
  • Receptors, Purinergic P2Y12
  • Sulfonamides
  • elinogrel
  • Clopidogrel
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT00751231