Abstract:Clinical efficacy of the antiplatelet drug clopidogrel is hampered by its variable biotransformation into the active metabolite. The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors, but the specific genes and mechanisms underlying clopidogrel bioactivation remain unclear. Using in vitro metabolomic profiling techniques, we identified paraoxonase-1 (PON1) as the crucial enzyme for clopidogrel bioactivation, with its common Q192R polymorphism determining the r… Show more
“…The authors calculated that the PON1 Q192R genotype may account for over 70% of the variability in platelet response to clopidogrel. 6 If this is confirmed, the major factor determining clopidogrel efficacy has been discovered; a landmark finding in pharmacogenomics.…”
Section: Beyond Cyp2c19 -A New Chapter In Clopidogrel Pharmacogenomicsmentioning
confidence: 99%
“…One hypothesis is that CYP2C19 genotype influences clinical outcomes independently of clopidogrel. 6 Despite these issues, the discovery of PON1 in the metabolic activation of clopidogrel is an exciting new chapter in clopidogrel pharmacogenomics. In addition to CYP2C19 and PON1, it is entirely plausible that novel variants in other key proteins that influence clopidogrel pharmacokinetics/pharmacodynamics are yet to be discovered, e.g.…”
Section: Beyond Cyp2c19 -A New Chapter In Clopidogrel Pharmacogenomicsmentioning
confidence: 99%
“…Bouman et al 6 report novel data in the January issue of Nature Medicine that challenges the current understanding of clopidogrel pharmacogenomics. A series of biochemical, clinical and epidemiological studies were conducted to support the conclusion that the enzyme paraoxonase-1 (PON1), rather than CYP2C19, is the major determinant of clopidogrel efficacy.…”
“…The authors calculated that the PON1 Q192R genotype may account for over 70% of the variability in platelet response to clopidogrel. 6 If this is confirmed, the major factor determining clopidogrel efficacy has been discovered; a landmark finding in pharmacogenomics.…”
Section: Beyond Cyp2c19 -A New Chapter In Clopidogrel Pharmacogenomicsmentioning
confidence: 99%
“…One hypothesis is that CYP2C19 genotype influences clinical outcomes independently of clopidogrel. 6 Despite these issues, the discovery of PON1 in the metabolic activation of clopidogrel is an exciting new chapter in clopidogrel pharmacogenomics. In addition to CYP2C19 and PON1, it is entirely plausible that novel variants in other key proteins that influence clopidogrel pharmacokinetics/pharmacodynamics are yet to be discovered, e.g.…”
Section: Beyond Cyp2c19 -A New Chapter In Clopidogrel Pharmacogenomicsmentioning
confidence: 99%
“…Bouman et al 6 report novel data in the January issue of Nature Medicine that challenges the current understanding of clopidogrel pharmacogenomics. A series of biochemical, clinical and epidemiological studies were conducted to support the conclusion that the enzyme paraoxonase-1 (PON1), rather than CYP2C19, is the major determinant of clopidogrel efficacy.…”
“…As I commented previously, 'a profession that is not actively engaged in research is stuck in the present (or, even worse, the past), is not looking to the future and is destined to become a dead profession'. 1 Other Considerations I have also benchmarked other aspects of pharmacy education in Australia against other countries. An important comparison is the number of pharmacy schools per capita.…”
Section: Research Intensity and Impactmentioning
confidence: 99%
“…1 In just 2 years, three more pharmacy schools have had pharmacy programs accredited! I believe that it is not possible for Australia to sustain 19 schools of pharmacy at standards relevant to delivery of high-quality pharmacy education to enable graduates to provide effective and safe pharmaceutical care to the Australian public.…”
Section: Pharmacovigilance For New Drugsmentioning
This case-control study identified 3 genes (CYP2C19, ABCB1, and ITGB3) and 2 clopidogrel-related factors (loading dose and proton pump inhibitors) that were independently associated with early stent thrombosis. Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts.
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