{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:26:04Z","timestamp":1780680364558,"version":"3.54.1"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This case report and literature review present two instances of delayed methotrexate clearance in individuals who were successfully managed using fixed dosing versus weight-based dosing of glucarpidase. These cases, along with existing literature, support the use of fixed-dose glucarpidase as an alternative to weight-based dosing for delayed methotrexate clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>Patient 1: a 26-year-old obese African American male with newly diagnosed osteosarcoma of the right distal fibula underwent his first cycle of neoadjuvant chemotherapy with MAP. Following the administration of doxorubicin and cisplatin, the patient developed acute kidney injury, with increased serum creatinine. He was admitted for high-dose methotrexate administration. Leucovorin rescue began 24 hours after high-dose methotrexate infusion. Twenty-five hours post-infusion, the patient had an elevated serum creatinine and methotrexate levels. A fixed dose of glucarpidase (2000 units) was administered, resulting in rapidly declining methotrexate levels and patient discharge. Patient 2: a 77-year-old obese white male with primary central nervous system lymphoma was admitted for cycle 3 of high-dose methotrexate and rituximab as first-line treatment. His pretreatment comorbidities included chronic kidney disease, coronary artery disease, hypertension, pulmonary hypertension, and chronic obstructive pulmonary disease. Following rituximab and high-dose methotrexate administration, nephrology was consulted owing to elevated creatinine. Leucovorin rescue began 24 hours after high-dose methotrexate treatment. On day 2, creatinine remained elevated with a post-dose methotrexate level indicating potential delayed clearance. A fixed dose of glucarpidase (2000 units) was administered, resulting in rapidly declining methotrexate levels and patient discharge. Cycle 4 was performed without complications, but cycle 5 required a fixed dose of glucarpidase owing to potential delayed clearance, resulting in rapidly declining methotrexate levels and patient discharge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients receiving high-dose methotrexate therapy requiring glucarpidase therapy, transitioning to a fixed dosing approach has significant cost-saving implications for institutions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13256-025-05774-2","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:04:54Z","timestamp":1772802294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effective high-dose methotrexate toxicity reversal using fixed-dose glucarpidase in obese patients: a case series"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7494-6225","authenticated-orcid":false,"given":"John","family":"Grofvert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Van Rossum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Pettijohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Mobayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon","family":"Stonerock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"issue":"12","key":"5774_CR1","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1200\/JCO.1987.5.12.2017","volume":"5","author":"SP Ackland","year":"1987","unstructured":"Ackland SP, Schilsky RL. High-dose methotrexate: a critical reappraisal. J Clin Oncol. 1987;5(12):2017\u201331. https:\/\/doi.org\/10.1200\/JCO.1987.5.12.2017.","journal-title":"J Clin Oncol"},{"issue":"10","key":"5774_CR2","doi-asserted-by":"publisher","first-page":"793","DOI":"10.2146\/ajhp130483","volume":"71","author":"M Fermiano","year":"2014","unstructured":"Fermiano M, Bergsbaken J, Kolesar JM. Glucarpidase for the management of elevated methotrexate levels in patients with impaired renal function. Am J Health Syst Pharm. 2014;71(10):793\u20138. https:\/\/doi.org\/10.2146\/ajhp130483.","journal-title":"Am J Health Syst Pharm"},{"issue":"2","key":"5774_CR3","first-page":"588","volume":"46","author":"LH Matherly","year":"1986","unstructured":"Matherly LH, Barlowe CK, Goldman ID. Antifolate polyglutamylation and competitive drug displacement at dihydrofolate reductase as important elements in leucovorin rescue in L1210 cells. 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Oncologist. 2007;12(11):1299\u2013308. https:\/\/doi.org\/10.1634\/theoncologist.12-11-1299.","journal-title":"Oncologist"},{"key":"5774_CR8","unstructured":"Glucarpidase [package insert]. Brentwood, TN: BTG International Inc.; 2012."},{"issue":"5","key":"5774_CR9","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.21873\/anticanres.16351","volume":"43","author":"T Kimura","year":"2023","unstructured":"Kimura T, Fukaya Y, Hamada Y, Yoshimura K, Kawamoto H. Pharmacokinetics and pharmacodynamics of glucarpidase rescue treatment after high-dose methotrexate therapy based on modeling and simulation. Anticancer Res. 2023;43(5):1919\u201324. https:\/\/doi.org\/10.21873\/anticanres.16351.","journal-title":"Anticancer Res"},{"issue":"5","key":"5774_CR10","first-page":"322","volume":"11","author":"S Trifilio","year":"2013","unstructured":"Trifilio S, Ma S, Petrich A. Reduced-dose carboxypeptidase-G2 successfully lowers elevated methotrexate levels in an adult with acute methotrexate-induced renal failure. Clin Adv Hematol Oncol. 2013;11(5):322\u20133.","journal-title":"Clin Adv Hematol Oncol"},{"issue":"3","key":"5774_CR11","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1002\/cpt.1957","volume":"108","author":"ZL Taylor","year":"2020","unstructured":"Taylor ZL, Mizuno T, Punt NC, et al. MTXPK.org: a clinical decision support tool evaluating high-dose methotrexate pharmacokinetics to inform post-infusion care and use of glucarpidase. Clin Pharmacol Ther. 2020;108(3):635\u201343. https:\/\/doi.org\/10.1002\/cpt.1957.","journal-title":"Clin Pharmacol Ther"},{"issue":"3","key":"5774_CR12","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1177\/0091270007311571","volume":"48","author":"M Phillips","year":"2008","unstructured":"Phillips M, Smith W, Balan G, Ward S. 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A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"193"}}