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This open\u2010label crossover study assessed the effect of fluoxetine on the pharmacological activity of clopidogrel in healthy volunteers. Eight healthy male volunteers received a single 600\u2010mg loading dose of clopidogrel followed by 20\u00a0mg of fluoxetine on 4\u00a0days and then 20\u00a0mg of fluoxetine plus 600\u00a0mg of clopidogrel on the fifth day. Eleven blood samples were withdrawn after clopidogrel administration to determine plasma concentrations of clopidogrel active metabolite (<jats:styled-content style=\"fixed-case\">CAM<\/jats:styled-content>) and platelet function. Platelet aggregation was measured by light transmittance aggregometry (<jats:styled-content style=\"fixed-case\">LTA<\/jats:styled-content>) and platelet reactivity index by flow cytometric vasodilator\u2010stimulated phosphoprotein (<jats:styled-content style=\"fixed-case\">VASP<\/jats:styled-content>) analysis. The areas under the curve and maximum plasma concentrations of <jats:styled-content style=\"fixed-case\">CAM<\/jats:styled-content> were, respectively, 20.6 and 25.3% lower after co\u2010administration of fluoxetine compared with administration of clopidogrel alone. The percentage maximum platelet aggregation values in the presence of 5\u00a0\u03bc<jats:sc>m<\/jats:sc> and 10\u00a0\u03bc<jats:sc>m<\/jats:sc> adenosine diphosphate, measured by <jats:styled-content style=\"fixed-case\">LTA<\/jats:styled-content>, were, respectively, 13.9 and 22.4% lower after fluoxetine co\u2010administration. The platelet reactivity index measured by the flow cytometric <jats:styled-content style=\"fixed-case\">VASP<\/jats:styled-content> method was 36.8% lower when clopidogrel was administered in conjunction with fluoxetine.<\/jats:p>","DOI":"10.1111\/fcp.12021","type":"journal-article","created":{"date-parts":[[2013,2,18]],"date-time":"2013-02-18T20:12:51Z","timestamp":1361218371000},"page":"683-689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Investigation of drug\u2013drug interactions between clopidogrel and fluoxetine"],"prefix":"10.1111","volume":"27","author":[{"given":"Xavier","family":"Delavenne","sequence":"first","affiliation":[{"name":"Laboratoire de Pharmacologie Toxicologie CHU Saint\u2010Etienne F\u201042055 Saint\u2010Etienne France"},{"name":"Universit\u00e9 de Lyon F\u201042023 Saint\u2010Etienne France"},{"name":"Groupe de Recherche sur la Thrombose EA3065 Universit\u00e9 de Saint\u2010Etienne 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