Efficacy of P2Y12 Receptor Blockers After Myocardial Infarction and Genetic Variability of their Metabolic Pathways

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F19%3A00071051" target="_blank" >RIV/00159816:_____/19:00071051 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/19:00109269

Výsledek na webu

<a href="https://www.ingentaconnect.com/content/ben/cvp/2019/00000017/00000001/art00009" target="_blank" >https://www.ingentaconnect.com/content/ben/cvp/2019/00000017/00000001/art00009</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1570161116666180206110657" target="_blank" >10.2174/1570161116666180206110657</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Efficacy of P2Y12 Receptor Blockers After Myocardial Infarction and Genetic Variability of their Metabolic Pathways

Popis výsledku v původním jazyce

Background: Various antiplatelet drugs are used following Acute Coronary Syndromes (ACS). Of them, adenosine diphosphate receptor P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor are currently used for post-ACS long-term treatment. Although they act on the same receptor, they differ in pharmacodynamics and pharmacokinetics. Several enzymes and transporters involved in the metabolism of P2Y12 inhibitors show genetic variability with functional impact. This includes P-glycoprotein, carboxylesterase 1 and, most notably, CYP2C19 that is important in clopidogrel activation. Common gain-of-function or loss-of-function alleles of CYP2C19 gene are associated with lower or higher platelet reactivity that may impact clinical outcomes of clopidogrel treatment. Prasugrel is considered to be less dependent on CYP2C19 variability as it is also metabolized by other CYP450 isoforms. Some studies, however, showed the relevance of CYP2C19 variants for platelet reactivity during prasugrel treatment as well. Ticagrelor is metabolized mainly by CYP3A4, which does not show functionally relevant genetic variability. Its concentrations may be modified by the variants of P-glycoprotein gene ABCB1. While no substantial difference between the clinical efficacy of prasugrel and ticagrelor has been documented, both of them have been shown to be superior to clopidogrel in post-ACS treatment. This can be partially explained by lower variability at each step of their metabolism. It is probable that factors influencing the pharmacokinetics of both drugs, including genetic factors, may predict the clinical efficacy of antiplatelet treatment in personalized medicine. Conclusion: We summarize the pharmacokinetics and pharmacogenetics of P2Y12 inhibitors with respect to their clinical effects in post-myocardial infarction treatment.

Název v anglickém jazyce

Efficacy of P2Y12 Receptor Blockers After Myocardial Infarction and Genetic Variability of their Metabolic Pathways

Popis výsledku anglicky

Background: Various antiplatelet drugs are used following Acute Coronary Syndromes (ACS). Of them, adenosine diphosphate receptor P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor are currently used for post-ACS long-term treatment. Although they act on the same receptor, they differ in pharmacodynamics and pharmacokinetics. Several enzymes and transporters involved in the metabolism of P2Y12 inhibitors show genetic variability with functional impact. This includes P-glycoprotein, carboxylesterase 1 and, most notably, CYP2C19 that is important in clopidogrel activation. Common gain-of-function or loss-of-function alleles of CYP2C19 gene are associated with lower or higher platelet reactivity that may impact clinical outcomes of clopidogrel treatment. Prasugrel is considered to be less dependent on CYP2C19 variability as it is also metabolized by other CYP450 isoforms. Some studies, however, showed the relevance of CYP2C19 variants for platelet reactivity during prasugrel treatment as well. Ticagrelor is metabolized mainly by CYP3A4, which does not show functionally relevant genetic variability. Its concentrations may be modified by the variants of P-glycoprotein gene ABCB1. While no substantial difference between the clinical efficacy of prasugrel and ticagrelor has been documented, both of them have been shown to be superior to clopidogrel in post-ACS treatment. This can be partially explained by lower variability at each step of their metabolism. It is probable that factors influencing the pharmacokinetics of both drugs, including genetic factors, may predict the clinical efficacy of antiplatelet treatment in personalized medicine. Conclusion: We summarize the pharmacokinetics and pharmacogenetics of P2Y12 inhibitors with respect to their clinical effects in post-myocardial infarction treatment.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Current vascular pharmacology

ISSN

1570-1611

e-ISSN

—

Svazek periodika

17

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

6

Strana od-do

35-40

Kód UT WoS článku

000459677100007

EID výsledku v databázi Scopus

—