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Efficacy of P2Y12 Receptor Blockers After Myocardial Infarction and Genetic Variability of their Metabolic Pathways.
- Source :
-
Current vascular pharmacology [Curr Vasc Pharmacol] 2019; Vol. 17 (1), pp. 35-40. - Publication Year :
- 2019
-
Abstract
- 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.<br />Conclusion: We summarize the pharmacokinetics and pharmacogenetics of P2Y12 inhibitors with respect to their clinical effects in post-myocardial infarction treatment.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B genetics
ATP Binding Cassette Transporter, Subfamily B metabolism
Animals
Biotransformation genetics
Blood Platelets metabolism
Clopidogrel adverse effects
Clopidogrel pharmacokinetics
Cytochrome P-450 CYP2C19 genetics
Cytochrome P-450 CYP2C19 metabolism
Cytochrome P-450 CYP3A genetics
Cytochrome P-450 CYP3A metabolism
Drug Resistance genetics
Humans
Myocardial Infarction blood
Myocardial Infarction diagnosis
Platelet Aggregation Inhibitors adverse effects
Platelet Aggregation Inhibitors pharmacokinetics
Prasugrel Hydrochloride adverse effects
Prasugrel Hydrochloride pharmacokinetics
Purinergic P2Y Receptor Antagonists adverse effects
Purinergic P2Y Receptor Antagonists pharmacokinetics
Receptors, Purinergic P2Y12 blood
Ticagrelor adverse effects
Ticagrelor pharmacokinetics
Treatment Outcome
Blood Platelets drug effects
Clopidogrel therapeutic use
Myocardial Infarction drug therapy
Pharmacogenomic Variants
Platelet Aggregation Inhibitors therapeutic use
Prasugrel Hydrochloride therapeutic use
Purinergic P2Y Receptor Antagonists therapeutic use
Receptors, Purinergic P2Y12 drug effects
Ticagrelor therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1875-6212
- Volume :
- 17
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Current vascular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 29412111
- Full Text :
- https://doi.org/10.2174/1570161116666180206110657