Efficacy of P2Y12 Receptor Blockers After Myocardial Infarction and Genetic Variability of their Metabolic Pathways
Language English Country United Arab Emirates Media print
Document type Journal Article, Review
PubMed
29412111
DOI
10.2174/1570161116666180206110657
PII: CVP-EPUB-88351
Knihovny.cz E-resources
- Keywords
- Myocardial infarction, clopidogrel, cytochrome P450, pharmacogenetic, pharmacokinetics, prasugrel, ticagrelor.,
- MeSH
- Biotransformation genetics MeSH
- Cytochrome P-450 CYP3A genetics metabolism MeSH
- Cytochrome P-450 CYP2C19 genetics metabolism MeSH
- Pharmacogenomic Variants * MeSH
- Myocardial Infarction blood diagnosis drug therapy MeSH
- Platelet Aggregation Inhibitors adverse effects pharmacokinetics therapeutic use MeSH
- Clopidogrel adverse effects pharmacokinetics therapeutic use MeSH
- Drug Resistance genetics MeSH
- Humans MeSH
- ATP Binding Cassette Transporter, Subfamily B genetics metabolism MeSH
- Prasugrel Hydrochloride adverse effects pharmacokinetics therapeutic use MeSH
- Purinergic P2Y Receptor Antagonists adverse effects pharmacokinetics therapeutic use MeSH
- Receptors, Purinergic P2Y12 blood drug effects MeSH
- Ticagrelor adverse effects pharmacokinetics therapeutic use MeSH
- Blood Platelets drug effects metabolism MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- ABCB1 protein, human MeSH Browser
- CYP2C19 protein, human MeSH Browser
- CYP3A4 protein, human MeSH Browser
- Cytochrome P-450 CYP3A MeSH
- Cytochrome P-450 CYP2C19 MeSH
- Platelet Aggregation Inhibitors MeSH
- Clopidogrel MeSH
- ATP Binding Cassette Transporter, Subfamily B MeSH
- P2RY12 protein, human MeSH Browser
- Prasugrel Hydrochloride MeSH
- Purinergic P2Y Receptor Antagonists MeSH
- Receptors, Purinergic P2Y12 MeSH
- Ticagrelor MeSH
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 Pglycoprotein, 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 Pglycoprotein 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.
Department of Pathophysiology Faculty of Medicine Masaryk University Brno Czech Republic
International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic
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