Optimizing clopidogrel dose response

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dc.contributor.author Saab, Yolande B.
dc.contributor.author Zeenny, Rony
dc.contributor.author Ramadan, Wijdan H.
dc.date.accessioned 2016-09-29T06:09:03Z
dc.date.available 2016-09-29T06:09:03Z
dc.date.issued 2016-09-29
dc.identifier.issn 1176-6336 en_US
dc.identifier.uri http://hdl.handle.net/10725/4442
dc.description.abstract Purpose Response to clopidogrel varies widely with nonresponse rates ranging from 4% to 30%. A reduced function of the gene variant of the CYP2C19 has been associated with lower drug metabolite levels, and hence diminished platelet inhibition. Drugs that alter CYP2C19 activity may also mimic genetic variants. The aim of the study is to investigate the cumulative effect of CYP2C19 gene polymorphisms and drug interactions that affects clopidogrel dosing, and apply it into a new clinical-pharmacogenetic algorithm that can be used by clinicians in optimizing clopidogrel-based treatment. Method Clopidogrel dose optimization was analyzed based on two main parameters that affect clopidogrel metabolite area under the curve: different CYP2C19 genotypes and concomitant drug intake. Clopidogrel adjusted dose was computed based on area under the curve ratios for different CYP2C19 genotypes when a drug interacting with CYP2C19 is added to clopidogrel treatment. A clinical-pharmacogenetic algorithm was developed based on whether clopidogrel shows 1) expected effect as per indication, 2) little or no effect, or 3) clinical features that patients experience and fit with clopidogrel adverse drug reactions. Results The study results show that all patients under clopidogrel treatment, whose genotypes are different from *1*1, and concomitantly taking other drugs metabolized by CYP2C19 require clopidogrel dose adjustment. To get a therapeutic effect and avoid adverse drug reactions, therapeutic dose of 75 mg clopidogrel, for example, should be lowered to 6 mg or increased to 215 mg in patients with different genotypes. Conclusion The implementation of clopidogrel new algorithm has the potential to maximize the benefit of clopidogrel pharmacological therapy. Clinicians would be able to personalize treatment to enhance efficacy and limit toxicity. en_US
dc.language.iso en en_US
dc.title Optimizing clopidogrel dose response en_US
dc.type Article en_US
dc.description.version Published en_US
dc.title.subtitle a new clinical algorithm comprising CYP2C19 pharmacogenetics and drug interactions en_US
dc.author.school SOP en_US
dc.author.idnumber 199110360 en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Therapeutics clinical risk management en_US
dc.journal.volume 11 en_US
dc.article.pages 1421-1427 en_US
dc.keywords Pharmacogenetics en_US
dc.keywords Genotype en_US
dc.keywords Genetic testing en_US
dc.keywords Individualized therapy en_US
dc.identifier.doi http://dx.doi.org/10.2147/TCRM.S83293 en_US
dc.identifier.ctation Saab, Y. B., Zeenny, R., & Ramadan, W. H. (2015). Optimizing clopidogrel dose response: a new clinical algorithm comprising CYP2C19 pharmacogenetics and drug interactions. Therapeutics and clinical risk management, 11, 1421. en_US
dc.author.email ysaab@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590670/ en_US

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