The effect of elinogrel on high platelet reactivity during dual antiplatelet therapy and the relation to CYP2C19*2 genotype: first experience in patients.

Published

Journal Article

To study the effect of a new direct acting reversible P2Y(12) inhibitor, elinogrel (PRT060128), and the relation to cytochrome P450 (CYP) polymorphisms in patients with high platelet reactivity (HPR) on standard dual antiplatelet therapy.We studied the pharmacodynamic and pharmacokinetic effects of a single 60-mg oral dose of elinogrel in 20 of 45 previously stented stable patients with HPR. We also genotyped for CYP2C19*2,3,5,17 and CYP3A5*3. Platelet reactivity fell within 4 h of dosing, the earliest time point evaluated as measured by the following assays: maximum 5 and 10 microM ADP LTA (P < 0.001 for both vs. predosing); maximum 20 microM ADP LTA (P < 0.05); VerifyNow (P < 0.001); thrombelastography (P < 0.05); VASP phosphorylation (P < 0.01); and perfusion chamber assay (P < 0.05); this was reversible within 24 h in these same assays (P = ns vs. predosing for all assays). CYP2C19*2 was present in 44% of all patients but was more frequent in HPR patients (77% vs. 16%, P = 0.0004).HPR is reversibly overcome by a single 60-mg oral dose of elinogrel, a drug now being investigated in a phase 2 trial. CYP2C19*2 was associated with HPR during conventional dual antiplatelet therapy.

Full Text

Duke Authors

Cited Authors

  • Gurbel, PA; Bliden, KP; Antonino, MJ; Stephens, G; Gretler, DD; Jurek, MM; Pakyz, RE; Shuldiner, AR; Conley, PB; Tantry, US

Published Date

  • January 2010

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 43 - 53

PubMed ID

  • 19817997

Pubmed Central ID

  • 19817997

Electronic International Standard Serial Number (EISSN)

  • 1538-7836

International Standard Serial Number (ISSN)

  • 1538-7933

Digital Object Identifier (DOI)

  • 10.1111/j.1538-7836.2009.03648.x

Language

  • eng