Evidence linking CYP2C19 to clopidogrel phenotype-Pharmacokinetics and
CYP2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 genotype impacts clopidogrel active metabolite formation
Clopidogrel is a prodrug that needs to be metabolized by the liver cytochrome P450 (CYP450) enzymes to be converted into an active drug
Individuals with a CYP2C19 PM phenotype have significantly reduced enzyme activity and cannot activate clopidogrel via CYP2C19, which means the drug will have a reduced
Taken together, our results suggest that CYP2C19 * 2 and * 3 variants influence the levels of RPA, MAR, sE-selectin, sCD40L, sP-selectin, MMP-9, and sVCAM
CYP2C19 gene has multiple single nucleotide polymorphism (SNP), which is the major determinant for clopidogrel treatment responses
In the case of CYP2C19, *1 is the normal or ‘wild-type’ allele with a Western-European allele frequency of 0
Several studies have shown that the effectiveness of clopidogrel for secondary stroke prevention is reduced among CYP2C19 LOF carriers
Pro227=) Gene: CYP2C19:cytochrome P450 family 2 subfamily C member 19 [Gene - OMIM - HGNC] Variant type: Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update
Scott SA, Sangkuhl K, Stein CM, Hulot JS, Mega JL, Roden DM, Klein TE
1 Clopidogrel is a prodrug dependent on the cytochrome P450 (CYP) 2C19 enzyme for bioactivation to its active
11–2
The purpose of this guideline is to provide clinicians with information that
39 Patients were randomized to either standard or genotype-guided therapy, which used a treatment algorithm that
alleles include the non-functional alleles *2 and *3, as well as the hyperactive *17 allele
CYP2C19 polymorphisms resulted in individual differences in clopidogrel response
Patients with two CYP2C19*1 (wild type) alleles metabolize Clopidogrel bisulfate efficiently (extensive metabolizers) and respond normally to Clopidogrel bisulfate therapy
1% (99/162) of patients and CYP2C19*3 was undetected
5% (40/63) of patients with CAD who are prescribed A recent study of a healthy population by Hulot et al
such as CYP2C19*1 Several studies have shown that the effectiveness of clopidogrel for secondary stroke prevention is reduced among CYP2C19 LOF carriers
The efficacy of clopidogrel is reduced in IM+PM, compared to EM patients
Clopidogrel therapy is standard of care for treating patients with coronary artery disease (CAD) and/or acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) [1, 2]