{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T23:06:24Z","timestamp":1784934384446,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>It was reported that high\u2010dose cyclosporine at 500\u00a0mg daily increases edoxaban exposure. We investigated whether cyclosporine &lt;500\u00a0mg daily leads to edoxaban\u2010induced bleeding in the clinical setting. This case series study included patients receiving edoxaban and cyclosporine at Mie University Hospital. The outcomes were bleeding and anticoagulant markers, including activated partial thromboplastin time (APTT), prothrombin time (PT), and the international normalized ratio of prothrombin time (PT\u2010INR). We examined the genotypes of cytochrome P450 3A5 (<jats:italic>CYP3A5<\/jats:italic>), multidrug resistance 1 (<jats:italic>ABCB1<\/jats:italic>), and solute carrier organic anion transporter 1B1 (<jats:italic>SLCO1B1<\/jats:italic>). Trends in anticoagulant markers were analyzed. Thirteen patients received edoxaban (standard dose; n\u00a0=\u00a03 and reduced dose; n\u00a0=\u00a010) and cyclosporine (1.94\u00a0\u00b1\u00a01.42\u00a0mg\/kg). A bleeding event occurred in one patient receiving a standard dose of edoxaban plus cyclosporine of 25\u00a0mg daily (HAS\u2010BLED score of 2 and genotypes; <jats:italic>CYP3A5*3\/*3<\/jats:italic>, <jats:italic>ABCB1 3435CT<\/jats:italic>, and <jats:italic>SLCO1B1*1a\/*1b<\/jats:italic>). After edoxaban treatment, anticoagulant markers were prolonged (APTT; 27.95\u00a0\u00b1\u00a03.64\u00a0s vs. 31.11\u00a0\u00b1\u00a03.90\u00a0s, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001, PT; 11.53\u00a0\u00b1\u00a01.01\u00a0s vs. 13.03\u00a0\u00b1\u00a00.98\u00a0s, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.002, PT\u2010INR; 0.98\u00a0\u00b1\u00a00.09 vs. 1.11\u00a0\u00b1\u00a00.11, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.007). In summary, the genotypes of <jats:italic>CYP3A5<\/jats:italic>, <jats:italic>ABCB1<\/jats:italic>, and <jats:italic>SLCO1B1<\/jats:italic> and the dosage of edoxaban may affect the risk of bleeding by edoxaban when co\u2010administered with cyclosporine, even at low doses.<\/jats:p>","DOI":"10.1002\/bdd.2332","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T03:04:20Z","timestamp":1664939060000},"page":"192-200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of bleeding and anticoagulation markers by edoxaban and low\u2010dose cyclosporine: A case series study"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3898-2068","authenticated-orcid":false,"given":"Toshinori","family":"Hirai","sequence":"first","affiliation":[{"name":"Department of Pharmacy Mie University Hospital Faculty of Medicine Mie University  Tsu Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Shinogi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mie University Hospital Faculty of Medicine Mie University  Tsu Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Ikejiri","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Mie University Hospital Faculty of Medicine Mie University  Tsu Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Murata","sequence":"additional","affiliation":[{"name":"Department of Nephrology Mie University Hospital Faculty of Medicine Mie University  Tsu Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-4410","authenticated-orcid":false,"given":"Takuya","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mie University Hospital 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