{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T07:42:09Z","timestamp":1698738129433},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,2,4]],"date-time":"2013-02-04T00:00:00Z","timestamp":1359936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label \/><jats:p>In this study, we assessed the effects of clopidogrel and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with <jats:italic>CYP2B6<\/jats:italic> polymorphisms in humans. Sibutramine showed enantioselective plasma profiles with consistently higher concentrations of <jats:italic>R<\/jats:italic>\u2010enantiomers. Clopidogrel and clarithromycin significantly increased the sibutramine plasma concentration, but their effects differed between enantiomers; a 2.2\u2010fold versus 4.1\u2010fold increase in the AUC in <jats:italic>S<\/jats:italic>\u2010enantiomer and 1.8\u2010fold versus 2.0\u2010fold for the <jats:italic>R<\/jats:italic>\u2010enantiomer, respectively. The AUCs of <jats:italic>S<\/jats:italic>\u2010 and <jats:italic>R<\/jats:italic>\u2010desmethyl metabolites changed significantly during the clopidogrel phase (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001 and <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001, respectively) but not during the clarithromycin phase (<jats:italic>P<\/jats:italic>\u2009=\u2009.099 and <jats:italic>P<\/jats:italic>\u2009=\u2009.090, respectively). Exposure to sibutramine was higher in subjects with the <jats:italic>CYP2B6*6\/*6<\/jats:italic> genotype, but no statistical difference was observed among the <jats:italic>CYP2B6<\/jats:italic> genotypes. These results suggest that the enantioselective disposition of sibutramine and its active metabolites are influenced by the altered genetic and environmental factors of CYP2B6 and CYP3A activity in vivo.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcph.69","type":"journal-article","created":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T20:48:49Z","timestamp":1361393329000},"page":"550-558","source":"Crossref","is-referenced-by-count":5,"title":["Different Effects of Clopidogrel and Clarithromycin on the Enantioselective Pharmacokinetics of Sibutramine and its Active Metabolites in Healthy Subjects"],"prefix":"10.1002","volume":"53","author":[{"given":"Dhananjay D.","family":"Shinde","sequence":"first","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center Inje University College of Medicine Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ho\u2010Sook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center Inje University College of Medicine Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae\u2010Seok","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center Inje University College of Medicine Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center Inje University College of Medicine Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Kyung","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center Inje University College of Medicine Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang\u2010Woo","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center Inje University College of Medicine Busan South Korea"},{"name":"Department of Clinical Pharmacology Inje University Busan Paik Hospital Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji\u2010Hong","family":"Shon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center Inje University College of Medicine Busan South Korea"},{"name":"Department of Clinical Pharmacology Inje University Busan Paik Hospital Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong\u2010Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center Inje University College of Medicine Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Gook","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and PharmacoGenomics Research Center Inje University College of Medicine Busan South Korea"},{"name":"Department of Clinical Pharmacology Inje University Busan Paik Hospital Busan South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,2,4]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"S18","article-title":"Sibutramine: a novel anti\u2010obesity drug. 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