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Metabolism and excretion involve cytochrome<jats:styled-content style=\"fixed-case\">P450 3A4<\/jats:styled-content>(<jats:styled-content style=\"fixed-case\">CYP3A4<\/jats:styled-content>) and<jats:styled-content style=\"fixed-case\">2J2<\/jats:styled-content>(<jats:styled-content style=\"fixed-case\">CYP2J2<\/jats:styled-content>),<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\u2010independent mechanisms, and<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010glycoprotein (<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010gp) and breast cancer resistance protein (<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>crp) (<jats:styled-content style=\"fixed-case\">ABCG2<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The pharmacokinetic effects of substrates or inhibitors of<jats:styled-content style=\"fixed-case\">CYP3A4<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010gp and<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>crp (<jats:styled-content style=\"fixed-case\">ABCG2<\/jats:styled-content>) on rivaroxaban were studied in healthy volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rivaroxaban did not interact with midazolam (<jats:styled-content style=\"fixed-case\">CYP3A4<\/jats:styled-content>probe substrate). Exposure to rivaroxaban when co\u2010administered with midazolam was slightly decreased by 11% (95% confidence interval [<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>] \u221228%, 7%) compared with rivaroxaban alone. The following drugs moderately affected rivaroxaban exposure, but not to a clinically relevant extent: erythromycin (moderate<jats:styled-content style=\"fixed-case\">CYP3A4<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010gp inhibitor; 34% increase [95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>23%, 46%]), clarithromycin (strong<jats:styled-content style=\"fixed-case\">CYP3A4<\/jats:styled-content>\/moderate<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010gp inhibitor; 54% increase [95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>44%, 64%]) and fluconazole (moderate<jats:styled-content style=\"fixed-case\">CYP3A4<\/jats:styled-content>, possible<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>crp [<jats:styled-content style=\"fixed-case\">ABCG2<\/jats:styled-content>] inhibitor; 42% increase [95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>29%, 56%]). A significant increase in rivaroxaban exposure was demonstrated with the strong<jats:styled-content style=\"fixed-case\">CYP3A4<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010gp\/<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>crp (<jats:styled-content style=\"fixed-case\">ABCG<\/jats:styled-content>2) inhibitors (and potential<jats:styled-content style=\"fixed-case\">CYP2J2<\/jats:styled-content>inhibitors) ketoconazole (158% increase [95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>136%, 182%] for a 400\u2009mg once daily dose) and ritonavir (153% increase [95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>134%, 174%]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Results suggest that rivaroxaban may be co\u2010administered with<jats:styled-content style=\"fixed-case\">CYP3A4<\/jats:styled-content>and\/or<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010gp substrates\/moderate inhibitors, but not with strong combined<jats:styled-content style=\"fixed-case\">CYP3A4<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\u2010gp and<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>crp (<jats:styled-content style=\"fixed-case\">ABCG2<\/jats:styled-content>) inhibitors (mainly comprising azole\u2010antimycotics, apart from fluconazole, and<jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>protease inhibitors), which are multi\u2010pathway inhibitors of rivaroxaban clearance and elimination.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12075","type":"journal-article","created":{"date-parts":[[2013,1,11]],"date-time":"2013-01-11T11:52:25Z","timestamp":1357905145000},"page":"455-466","source":"Crossref","is-referenced-by-count":329,"title":["Co\u2010administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects"],"prefix":"10.1111","volume":"76","author":[{"given":"Wolfgang","family":"Mueck","sequence":"first","affiliation":[{"name":"Bayer HealthCare Pharmaceuticals Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Kubitza","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Pharmaceuticals Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Becka","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Pharmaceuticals Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01166.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02429.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH06-11-0620"},{"key":"e_1_2_10_5_1","first-page":"Abstract P2943","article-title":"Antithrombotic efficacy of BAY 59\u20107939 \u2013 an oral, direct Factor Xa inhibitor \u2013 compared with fondaparinux in animal arterial thrombosis and thromboembolic death models","volume":"26","author":"Perzborn E","year":"2005","journal-title":"Eur Heart J"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH10-09-0601"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1007903"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113572"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009638"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112277"},{"key":"e_1_2_10_11_1","unstructured":"Xarelto\u00ae (rivaroxaban).Bayer Pharma AG Summary of Product Characteristics.2012. 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