Identification and Biological Activity of the Active Metabolite of Clopidogrel

By P. Savi, J. Pereillo, Marie-Françoise Uzabiaga, J. Combalbert, C. Picard, J. Maffrand, M. Pascal, J. Herbert. Thrombosis and Haemostasis, 2000

780 citations recorded by the source corpus.

Subfields: Cardiology and Cardiovascular Medicine, Pharmacology

View Paper: https://www.semanticscholar.org/paper/f706f8321b3abe5af6d1e24783e54d69946a17d1

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In Cardiology and Cardiovascular Medicine

1. Peter C. Austin
2. E. Braunwald
3. Roger Mundry

In Pharmacology

1. Shufeng Zhou
2. Jun-Ping Liu
3. B. Chowbay

Citations in the corpus

• Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. (2005, background): “Clopidogrel is a prodrug that is metabolized in the liver by the cytochrome P450 system into its active form.(16) In the absence of a loading dose, Table 3.”
• Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin α2β1 (2003, background): “Furthermore, involvement of disulfide exchange in adhesive receptor function is a feature specific to the integrin receptor family (12) though other receptors may contribute to this process (13-15).”
• International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy (2006, background): “Clopidogrel (31) produces a metabolite (32), which acts as an irreversible P2Y12 receptor antagonist (Savi et al., 2000).”
• Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. (2009, background): “sion of clopidogrel to its active metabolite.(4,5,17,18,32-35) A guanine adenine mutation in exon 5 of CYP2C19 ( r s4244285 , a l so known as CYP2C19*2) creates an aberrant splice site that leads to an altered reading frame at amino acid 215 and a premature stop codon 20 amino acids downstream, prod”
• Identification of the Human Cytochrome P450 Enzymes Involved in the Two Oxidative Steps in the Bioactivation of Clopidogrel to Its Pharmacologically Active Metabolite (2010, background): “1 (Savi et al., 2000).”
• Polymorphism of human cytochrome P450 enzymes and its clinical impact (2009, background): “Multiple CYPs catalyze the oxidation of the thiophene ring of clopidogrel to 2-oxoclopidogrel, which is then hydrolyzed by opening of the thiophene ring to form both a carboxyl and a thiol group (Savi et al., 2000).”
• A population-based study of the drug interaction between proton pump inhibitors and clopidogrel (2009, background): “Clopidogrel is a prodrug that is converted in the liver to an active thiol metabolite, which irreversibly inhibits the platelet P2Y12 adenosine diphosphate receptor.(6,7) This bioactivation is mediated by hepatic cytochrome P450 isoenzymes, with cytochrome P450 2C19 playing a major role.”