{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:39:04Z","timestamp":1790005144109,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T00:00:00Z","timestamp":1532649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001009","name":"Bristol-Myers Squibb Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM008562"],"award-info":[{"award-number":["T32GM008562"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>Apixaban is metabolized by cytochrome P450 (<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>) 3A4 in the liver and intestine, undergoes direct intestinal excretion, and is a substrate to permeability glycoprotein (P\u2010gp) and breast cancer resistance protein (<jats:styled-content style=\"fixed-case\">BCRP<\/jats:styled-content>) transporters. We examined the drug interactions between cyclosporine and tacrolimus (combined inhibitors of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4, P\u2010gp, and <jats:styled-content style=\"fixed-case\">BCRP<\/jats:styled-content>) with apixaban in 12 healthy adult male volunteers. Apixaban 10\u00a0mg was administered orally alone, in combination with 100\u00a0mg cyclosporine or 5\u00a0mg tacrolimus. Co\u2010administration with cyclosporine resulted in increase in apixaban maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) and area under the plasma concentration\u2010time curve from time zero to the last quantifiable concentration (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>(0\u2010tlast)<\/jats:sub>) with associated geometric mean ratios (<jats:styled-content style=\"fixed-case\">GMRs<\/jats:styled-content>) and 90% confidence intervals (<jats:styled-content style=\"fixed-case\">CIs<\/jats:styled-content>) of 143% (112, 183) and 120% (97, 148), respectively. Co\u2010administration with tacrolimus resulted in reduction in apixaban <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> and <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>(0\u2010tlast)<\/jats:sub> with associated <jats:styled-content style=\"fixed-case\">GMR<\/jats:styled-content>s (90% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) of 87% (69, 112) and 78% (63, 97), respectively. The observed changes in apixaban exposure margins with cyclosporine or tacrolimus are within the range of the historical clinical development program, therefore, apixaban dose adjustments are not warranted.<\/jats:p>","DOI":"10.1111\/cts.12580","type":"journal-article","created":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T14:31:23Z","timestamp":1530628283000},"page":"590-596","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Drug\u2010Drug Interaction Study of Apixaban with Cyclosporine and Tacrolimus in Healthy Volunteers"],"prefix":"10.1111","volume":"11","author":[{"given":"Babar","family":"Bashir","sequence":"first","affiliation":[{"name":"Department of Pharmacologyand Experimental Therapeutics Thomas Jefferson University  Philadelphia Pennsylvania USA"},{"name":"Department of Medical Oncology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas F.","family":"Stickle","sequence":"additional","affiliation":[{"name":"Department of Pathology Thomas Jefferson University Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Chervoneva","sequence":"additional","affiliation":[{"name":"Department of Pharmacologyand Experimental Therapeutics Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter K.","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Pharmacologyand Experimental Therapeutics Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,27]]},"reference":[{"key":"e_1_2_10_1_1","first-page":"17","article-title":"The use of cyclosporin A and prednisone in cadaver kidney transplantation","volume":"1","author":"Starzl T.E.","year":"1980","journal-title":"Surg. 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