TY - JOUR
T1 - Pharmacokinetic and pharmacodynamic effects of elinogrel
T2 - 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
AU - Angiolillo, Dominick J.
AU - Welsh, Robert C.
AU - Trenk, Dietmar
AU - Neumann, Franz Josef
AU - Conley, Pamela B.
AU - McClure, Matthew W.
AU - Stephens, Gillian
AU - Kochman, Janusz
AU - Jennings, Lisa K.
AU - Gurbel, Paul A.
AU - Wójcik, Jaroslaw
AU - Dabrowski, Marek
AU - Saucedo, Jorge F.
AU - Stumpf, Juergen
AU - Buerke, Michael
AU - Broderick, Samuel
AU - Harrington, Robert A.
AU - Rao, Sunil V.
PY - 2012/6
Y1 - 2012/6
N2 - Background-Elinogrel is the only selective, competitive and reversible platelet P2Y inhibitor available in both intravenous (IV) and oral formulations. 12 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.
AB - Background-Elinogrel is the only selective, competitive and reversible platelet P2Y inhibitor available in both intravenous (IV) and oral formulations. 12 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.
KW - Elinogrel
KW - Pharmacodynamics
KW - Pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=84864620660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864620660&partnerID=8YFLogxK
U2 - 10.1161/CIRCINTERVENTIONS.111.965608
DO - 10.1161/CIRCINTERVENTIONS.111.965608
M3 - Article
C2 - 22619259
AN - SCOPUS:84864620660
SN - 1941-7640
VL - 5
SP - 347
EP - 356
JO - Circulation: Cardiovascular Interventions
JF - Circulation: Cardiovascular Interventions
IS - 3
ER -