{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:37:40Z","timestamp":1786977460104,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016275","name":"Seoul National University Bundang Hospital","doi-asserted-by":"publisher","award":["14\u20102022\u20100046"],"award-info":[{"award-number":["14\u20102022\u20100046"]}],"id":[{"id":"10.13039\/100016275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>\n                    Methotrexate (MTX) is an antifolate agent widely used for treating conditions such as rheumatoid arthritis and hematologic cancer. This study aimed to quantitatively interpret the drug\u2013drug interactions (DDIs) of MTX mediated by drug transporters using physiologically\u2010based pharmacokinetic (PBPK) modeling. An open\u2010label, randomized, 4\u2010treatment, 6\u2010sequence, 4\u2010period crossover study was conducted to investigate the effects of rifampicin (RFP), an inhibitor of organic anionic transporting peptides (OATP) 1B1\/3, and febuxostat (FBX), an inhibitor of breast cancer resistance protein (BCRP), on the pharmacokinetics of MTX in healthy volunteers. PBPK models of MTX, RFP, and FBX were developed based on\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    data, and the performance of the simulation results for final PBPK models was validated in a clinical study. In the clinical study, when MTX was co\u2010administered with RFP or FBX, systemic exposure of MTX increased by 33% and 17%, respectively, compared with that when MTX was administered alone. When MTX was co\u2010administered with RFP and FBX, systemic exposure increased by 52% compared with that when MTX was administered alone. The final PBPK model showed a good prediction performance for the observed clinical data. The PBPK model of MTX was well developed in this study and can be used as a potential mechanistic model to predict and evaluate drug transporter\u2010mediated DDIs of MTX with other drugs.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3329","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T04:59:39Z","timestamp":1718081979000},"page":"1013-1022","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Comprehensive Evaluation of\n                    <scp>OATP<\/scp>\n                    \u2010 and\n                    <scp>BCRP<\/scp>\n                    \u2010Mediated Drug\u2013Drug Interactions of Methotrexate Using Physiologically\u2010Based Pharmacokinetic Modeling"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0154-5777","authenticated-orcid":false,"given":"Sejung","family":"Hwang","sequence":"first","affiliation":[{"name":"Department 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