{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:55:32Z","timestamp":1787068532770,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR001425"],"award-info":[{"award-number":["UL1TR001425"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K08 CA263482"],"award-info":[{"award-number":["K08 CA263482"]}],"id":[{"id":"10.13039\/100000054","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":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mtxpk.org\">MTXPK.org<\/jats:ext-link>\n                    webtool was launched in December 2019 and was developed to facilitate model\u2010informed supportive care and optimal use of glucarpidase following the administration of high\u2010dose methotrexate (HDMTX). One limitation identified during the original development of the\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mtxpk.org\">MTXPK.org<\/jats:ext-link>\n                    tool was the perceived generalizability because the modeled population comprised solely of Nordic pediatric patients receiving 24\u2010h infusions for the treatment of acute lymphoblastic leukemia. The goal of our study is to describe the pharmacokinetics of HDMTX from a diverse patient population (e.g., races, ethnicity, indications for methotrexate, and variable infusion durations) and identify meaningful factors that account for methotrexate variability and improve the model's performance. To do this, retrospectively analyzed pharmacokinetic and toxicity data from pediatric and adolescent young adult patients who were receiving HDMTX (&gt;0.5\u2009g\/m\n                    <jats:sup>2<\/jats:sup>\n                    ) for the treatment of a cancer diagnosis from three pediatric medical centers. We performed population pharmacokinetic modeling referencing the original\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mtxpk.org\">MTXPK.org<\/jats:ext-link>\n                    NONMEM model (includes body surface area and serum creatinine as covariates) on 1668 patients, 7506 administrations of HDMTX, and 30,250 concentrations. Our results support the parameterizations of short infusion duration (&lt;8\u2009h) and the presence of Down syndrome on methotrexate clearance, the parameterization of severe hypoalbuminemia (&lt;2.5\u2009g\/dL) on the intercompartmental clearance (Q2 and Q3), and the parameterization of pleural effusion on the volume of distribution (V1 and V2). These novel parameterizations will increase the generalizability of the\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mtxpk.org\">MTXPK.org<\/jats:ext-link>\n                    model once they are added to the webtool.\n                  <\/jats:p>","DOI":"10.1111\/cts.13600","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T07:50:09Z","timestamp":1690530609000},"page":"2130-2143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Clinical covariates that improve the description of high dose methotrexate pharmacokinetics in a diverse population to inform MTXPK.org"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-2397","authenticated-orcid":false,"given":"Zachary L.","family":"Taylor","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4250-5376","authenticated-orcid":false,"given":"Tamara P.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Emory University School of Medicine  Atlanta Georgia USA"},{"name":"Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6805-2243","authenticated-orcid":false,"given":"Ethan A.","family":"Poweleit","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Division of Research in Patient Services Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Biomedical Informatics University of Cincinnati  Cincinnati Ohio USA"},{"name":"Division of Biomedical Informatics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"DeGroote","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8760-5202","authenticated-orcid":false,"given":"Lauren","family":"Pommert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Oncology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio 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Disorders Center of Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Ambrosino","sequence":"additional","affiliation":[{"name":"Division of Oncology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Chavana","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9612-3624","authenticated-orcid":false,"given":"Melanie B.","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric 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