{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T21:28:21Z","timestamp":1760909301522,"version":"3.40.5"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K07150"],"award-info":[{"award-number":["20K07150"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:p>The effects of polymorphisms of <jats:italic>ABCB1<\/jats:italic> and <jats:italic>ABCG2<\/jats:italic> on the dose\u2010adjusted plasma trough concentrations and cerebrospinal fluid (CSF)\u2010to\u2010plasma ratios of ponatinib were evaluated. Blood (C<jats:sub>4<\/jats:sub>) and CSF (CSF<jats:sub>4<\/jats:sub>) concentrations at 4\u00a0h after administration were determined. The median (95% confidence interval) CSF<jats:sub>4<\/jats:sub>\u2010to\u2010C<jats:sub>4<\/jats:sub> ratio of ponatinib in subjects homozygous for <jats:italic>ABCB1<\/jats:italic> variants 1236T\/T, 2677T\/T\u2009+\u2009T\/A or 3435T\/T were significantly higher than that in a group of subjects with other genotypes (<jats:italic>P<\/jats:italic>\u2009=\u2009.026, .012 and .015, respectively). The median (95% confidence interval) CSF<jats:sub>4<\/jats:sub>\u2010to\u2010C<jats:sub>4<\/jats:sub> ratio of ponatinib in 4 patients with the combination of <jats:italic>ABCB1<\/jats:italic> variants 1236T\/T\u20102677T\/T\u2009+\u2009T\/A\u20103435T\/T was 2.62% (1.42\u20133.42%); this ratio was significantly higher than that in subjects with other genotypes (1.08% [0.89\u20131.47%]; <jats:italic>P<\/jats:italic>\u2009=\u2009.006). The brain distribution of ponatinib was affected by <jats:italic>ABCB1<\/jats:italic> polymorphisms and therefore seems to be modulated by P\u2010glycoprotein at the blood\u2013brain and blood\u2013CSF barriers.<\/jats:p>","DOI":"10.1111\/bcp.15650","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T09:11:34Z","timestamp":1671613894000},"page":"1695-1700","source":"Crossref","is-referenced-by-count":3,"title":["Effects of <i>ABCB1<\/i> polymorphisms on the transport of ponatinib into the cerebrospinal fluid in Japanese Philadelphia chromosome\u2010positive acute lymphoblastic leukaemia patients"],"prefix":"10.1111","volume":"89","author":[{"given":"Yayoi","family":"Fukushi","sequence":"first","affiliation":[{"name":"Department of Pharmacy Akita University Hospital  1\u20101\u20101 Hondo Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiko","family":"Akamine","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Akita University Hospital  1\u20101\u20101 Hondo Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiko","family":"Abumiya","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Akita University Hospital  1\u20101\u20101 Hondo Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagi","family":"Tozawa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Nephrology, and Rheumatology Akita University Graduate School of Medicine  Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaya","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Hematology, Nephrology, and Rheumatology Akita University Graduate School of Medicine  Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miho","family":"Nara","sequence":"additional","affiliation":[{"name":"Department of Hematology, Nephrology, and Rheumatology Akita 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