{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:10:02Z","timestamp":1777421402109,"version":"3.51.4"},"reference-count":22,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20H05798"],"award-info":[{"award-number":["20H05798"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The breast cancer resistance protein (BCRP) is a key drug transporter found in the liver, kidney, central nervous system, and gastrointestinal tract. Due to the wide expression of BCRP, interactions of other drugs with methotrexate (MTX) may differ in oral and intravenous MTX users, and understanding of these interactions may be useful in preventing severe adverse events. Febuxostat, a urate-lowering drug, inhibits BCRP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The objective of this study was to clarify the differences in the drug-drug interaction profiles of oral and intravenous methotrexate, associated with BCRP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We analyzed the Japanese Adverse Drug Event Report database and compared the frequency of hematologic events in patients taking oral and intravenous MTX, with or without the concomitant use of febuxostat or allopurinol. Hematologic events were defined as pancytopenia and neutropenia. Multiple logistic regression analysis was then used to identify the risk factors for hematologic events in oral and intravenous MTX users.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We identified 8 453 oral and 810 intravenous MTX users with 546 and 126 cases of hematologic events, respectively. Compared with those not using febuxostat, a disproportionate number of hematologic events was observed in intravenous MTX users concomitantly using febuxostat (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01). The multivariate logistic analysis of intravenous MTX users showed that hematologic events were significantly associated with febuxostat use (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01) and age \u2265 60 years (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Relevance:<\/jats:title>\n                    <jats:p>Our findings suggest that patients being treated with intravenous MTX who concomitantly use febuxostat may be at an increased risk of hematologic events, presumably due to BCRP-mediated drug-drug interaction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10600280211055794","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T05:12:35Z","timestamp":1635829955000},"page":"910-915","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Risk of Hematologic Events With Coadministration of Methotrexate and the Breast Cancer Resistance Protein Inhibitor Febuxostat"],"prefix":"10.1177","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-1253","authenticated-orcid":false,"given":"Satoru","family":"Mitsuboshi","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Kaetsu Hospital, Niigata, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Niimura","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology &amp; Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaya","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology &amp; Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan"},{"name":"Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunsuke","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshito","family":"Zamami","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology &amp; Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan"},{"name":"Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Ishizawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology &amp; Therapeutics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan"},{"name":"Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"issue":"2","key":"e_1_3_2_2_2","first-page":"272","article-title":"Outcomes related to methotrexate dose and route of administration in patients with rheumatoid arthritis: a systematic literature review","volume":"33","author":"Goodman SM","year":"2015","unstructured":"Goodman SM, Cronstein BN, Bykerk VP. 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