Document Detail


Modification of the VerifyNow® P2Y12 test BASE channel to accommodate high levels of P2Y(12) antagonism.
MedLine Citation:
PMID:  21639823     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The VerifyNow® P2Y12 (VN-P2Y12) test reports thienopyridine-mediated platelet inhibition relative to a "BASE" channel, potentially eliminating the need for predrug patient assessment, by activating platelets through a P2Y(12)-independent pathway. The original formulation of the BASE channel used a protease activated receptor-1 (PAR-1) peptide as agonist. However, more potent P2Y(12) antagonism required more complete activation of platelet thrombin receptors for the BASE measurement in order to negate any contribution of the P2Y(12) receptor. Accordingly, the current BASE channel formulation consists of both PAR-1 and protease activated receptor-4 (PAR-4) activating peptides to facilitate a higher degree of platelet activation. The aim of this study was to compare the performance of PAR-1 versus PAR-1/PAR-4 activating peptides as the BASE channel formulation using prasugrel's active metabolite, R-138727, in vitro to achieve high-grade P2Y(12) inhibition. Blood samples from 20 healthy donors were spiked in vitro with R-138727 at concentrations that include plasma levels achieved following prasugrel administration and were incubated for 30 minutes at 37°C. All samples were run in triplicate using both the PAR-1 and the PAR-1/PAR-4 BASE formulation in the VN-P2Y12 test device. The data confirmed the sensitivity of the original BASE formulation to high-grade P2Y(12) inhibition as reflected in the concentration-dependent decrease in values. Incorporation of PAR-4 activating peptide eliminated the effect of P2Y(12) blockade at all concentrations of R-138727. Thus, the use of PAR-1/PAR-4 in the BASE channel of the VN-P2Y12 cartridge addresses the impact of high grade P2Y(12) blockade and may allow more accurate reporting of "% inhibition" in patients treated with more effective P2Y(12) antagonists.
Authors:
Joseph A Jakubowski; Chunmei Zhou; Blaine Egan; Maggie Wells; Maya Kotob-Yahfoufi; Atsuhiro Sugidachi; Jeffrey R Dahlen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-6
Journal Detail:
Title:  Platelets     Volume:  -     ISSN:  1369-1635     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208117     Medline TA:  Platelets     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company , Indianapolis, IN , USA.
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