{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T20:47:33Z","timestamp":1783543653619,"version":"3.55.0"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Wellstat Therapeutics"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2018,8]]},"DOI":"10.1016\/j.taap.2018.06.012","type":"journal-article","created":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T17:15:14Z","timestamp":1528996514000},"page":"67-73","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Prompt treatment with uridine triacetate improves survival and reduces toxicity due to fluorouracil and capecitabine overdose or dihydropyrimidine dehydrogenase deficiency"],"prefix":"10.1016","volume":"353","author":[{"given":"Rolando A.G.","family":"Garcia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel A.","family":"Saydoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Bamat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reid W.","family":"von Borstel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2018.06.012_bb0005","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1007\/s00280-006-0213-x","article-title":"Modulation of 5-fluorouracil host-toxicity and chemotherapeutic efficacy against human colon tumors by 5-(Phenylthio)acyclouridine, a uridine phosphorylase inhibitor","volume":"58","author":"Al Safarjalani","year":"2006","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.taap.2018.06.012_bb0010","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1007\/s00280-012-1842-x","article-title":"Potent combination therapy for human breast tumors with high doses of 5-fluorouracil: remission and lack of host toxicity","volume":"69","author":"Al Safarjalani","year":"2012","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.taap.2018.06.012_bb0015","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/0006-2952(96)00102-5","article-title":"5-(m-Benzyloxybenzyl)barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2\u2032,3\u2032,5\u2032-tri-O-acetyluridine, a prodrug of uridine, as modulators of plasma uridine concentration","volume":"51","author":"Ashour","year":"1996","journal-title":"Implications for chemotherapy, Biochem Pharmacol"},{"key":"10.1016\/j.taap.2018.06.012_bb0020","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0006-2952(00)00342-7","article-title":"Modulation of 5-fluorouracil host toxicity by 5- (benzyloxybenzyl)barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2\u2032,3\u2032,5\u2032-tri-O-acetyluridine, a prodrug of uridine","volume":"60","author":"Ashour","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.taap.2018.06.012_bb0025","doi-asserted-by":"crossref","first-page":"11064","DOI":"10.1073\/pnas.90.23.11064","article-title":"5-Ethynyluracil (776C85): a potent modulator of the pharmacokinetics and antitumor efficacy of 5-fluorouracil","volume":"90","author":"Baccanari","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.taap.2018.06.012_bb0030","first-page":"309","article-title":"Modulation of 5-fluorouracil in mice using uridine diphosphoglucose","volume":"3","author":"Codacci-Pisanelli","year":"1997","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.taap.2018.06.012_bb0035","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1159\/000065069","article-title":"High-dose 5-Fluorouracil with uridine-diphosphoglucose rescue increases thymidylate synthase inhibition but not 5-Fluorouracil incorporation into RNA in murine tumors","volume":"62","author":"Codacci-Pisanelli","year":"2002","journal-title":"Oncology"},{"key":"10.1016\/j.taap.2018.06.012_bb0040","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1021\/op0100100","article-title":"Process Research and development of a dihydropyrimidine dehydrogenase inactivator: large-scale preparation of eniluracil using a sonogashira coupling","volume":"5","author":"Cooke","year":"2001","journal-title":"Org. Process Res. Dev."},{"key":"10.1016\/j.taap.2018.06.012_bb0045","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s10637-006-9244-8","article-title":"Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: a southwest oncology group study","volume":"24","author":"Doroshow","year":"2006","journal-title":"Investig. New Drugs"},{"key":"10.1016\/j.taap.2018.06.012_bb0050","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3816\/CCC.2004.n.018","article-title":"Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration","volume":"4","author":"Ezzeldin","year":"2004","journal-title":"Clin. Colorectal Cancer"},{"key":"10.1016\/j.taap.2018.06.012_bb0055","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/ijc.29025","article-title":"Clinical importance of risk variants in the dihydropyrimidine dehydrogenase gene for the prediction of early-onset fluoropyrimidine toxicity","volume":"136","author":"Froehlich","year":"2015","journal-title":"Int. J. Cancer"},{"issue":"4","key":"10.1016\/j.taap.2018.06.012_bb0060","first-page":"533","article-title":"Qualitative and quantitative toxicity of single and sequential sublethal doses of 5-fluorouracil in BDF mice","volume":"62","author":"Harrison","year":"1978","journal-title":"Cancer Treatment Reports"},{"key":"10.1016\/j.taap.2018.06.012_bb0065","doi-asserted-by":"crossref","first-page":"3928","DOI":"10.1158\/1078-0432.CCR-05-2665","article-title":"Orotate phosphoribosyltransferase gene polymorphism predicts toxicity in patients treated with bolus 5-fluorouracil regimen","volume":"12","author":"Ichikawa","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.taap.2018.06.012_bb0070","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.1158\/1078-0432.CCR-16-0638","article-title":"FDA approval: uridine triacetate for the treatment of patients following fluorouracil or capecitabine overdose or exhibiting early-onset severe toxicities following administration of these drugs","volume":"22","author":"Ison","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.taap.2018.06.012_bb0075","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1200\/JCO.1997.15.4.1511","article-title":"Phase I trial of PN401, an oral prodrug of uridine, to prevent toxicity from fluorouracil in patients with advanced cancer","volume":"15","author":"Kelsen","year":"1997","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.taap.2018.06.012_bb0080","first-page":"3182","article-title":"Use of uridine rescue to enhance the antitumor selectivity of 5- fluorouracil","volume":"43","author":"Klubes","year":"1983","journal-title":"Cancer Res."},{"key":"10.1016\/j.taap.2018.06.012_bb0085","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1007\/BF00256691","article-title":"Comparison of the bioavailability of uridine in mice after either oral or parenteral administration","volume":"17","author":"Klubes","year":"1986","journal-title":"Cancer Chemother. Pharmacol."},{"issue":"2","key":"10.1016\/j.taap.2018.06.012_bb0090","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/cncr.30321","article-title":"Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity","volume":"123","author":"Ma","year":"2017","journal-title":"Cancer"},{"key":"10.1016\/j.taap.2018.06.012_bb0095","first-page":"3964","article-title":"High-dose 5-fluorouracil with delayed uridine \"rescue\" in mice","volume":"42","author":"Martin","year":"1982","journal-title":"Cancer Res."},{"key":"10.1016\/j.taap.2018.06.012_bb0100","first-page":"4653","article-title":"Improved therapeutic index with sequential N-phosphonacetyl-L-aspartate plus high-dose methotrexate plus high-dose 5-fluorouracil and appropriate rescue","volume":"43","author":"Martin","year":"1983","journal-title":"Cancer Res."},{"key":"10.1016\/j.taap.2018.06.012_bb0105","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/BF00254098","article-title":"Use of oral uridine as a substitute for parenteral uridine rescue of 5- fluorouracil therapy, with and without the uridine phosphorylase inhibitor 5-benzylacyclouridine","volume":"24","author":"Martin","year":"1989","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.taap.2018.06.012_bb0110","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/S0021-5198(19)52945-6","article-title":"Cardiotoxic effects of 5-fluorouracil in the guinea pig","volume":"30","author":"Matsubara","year":"1980","journal-title":"Jpn. J. Pharmacol."},{"key":"10.1016\/j.taap.2018.06.012_bb0115","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s00280-008-0889-1","article-title":"Early severe toxicities after capecitabine intake: possible implication of a cytidine deaminase extensive metabolizer profile","volume":"63","author":"Mercier","year":"2009","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.taap.2018.06.012_bb0120","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ejca.2015.10.013","article-title":"Renal function, body surface area, and age are associated with risk of early-onset fluoropyrimidine-associated toxicity in patients treated with capecitabine-based anticancer regimens in daily clinical care","volume":"54","author":"Meulendijks","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"10.1016\/j.taap.2018.06.012_bb0125","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1139\/m91-037","article-title":"Induction of lethal infection with indigenous Escherichia coli in mice by fluorouracil","volume":"37","author":"Nomoto","year":"1991","journal-title":"Can. J. Microbiol."},{"key":"10.1016\/j.taap.2018.06.012_bb0130","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1016\/0006-2952(92)90142-6","article-title":"Biochemical modulation of 5-fluorouracil with leucovorin or delayed uridine rescue. Correlation of antitumor activity with dosage and FUra incorporation into RNA","volume":"43","author":"Nord","year":"1992","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.taap.2018.06.012_bb0135","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/bjc.1988.56","article-title":"In vitro biochemical and in vivo biological studies of the uridine 'rescue' of 5-fluorouracil","volume":"57","author":"Peters","year":"1988","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.taap.2018.06.012_bb0140","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.ctrv.2013.03.005","article-title":"Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: a systematic review of incidence, manifestations and predisposing factors","volume":"39","author":"Polk","year":"2013","journal-title":"Cancer Treat. Rev."},{"key":"10.1016\/j.taap.2018.06.012_bb0145","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-012798","article-title":"Incidence and risk factors for capecitabine-induced symptomatic cardiotoxicity: a retrospective study of 452 consecutive patients with metastatic breast cancer","volume":"6","author":"Polk","year":"2016","journal-title":"BMJ Open"},{"key":"10.1016\/j.taap.2018.06.012_bb0150","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1073\/pnas.94.5.1795","article-title":"Inhibition by uridine but not thymidine of p53-dependent intestinal apoptosis initiated by 5-fluorouracil: evidence for the involvement of RNA perturbation","volume":"94","author":"Pritchard","year":"1997","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.taap.2018.06.012_bb0155","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s00280-005-0129-x","article-title":"5-fluorouracil dose escalation enabled with PN401 (triacetyluridine): toxicity reduction and increased antitumor activity in mice","volume":"58","author":"Saif","year":"2006","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.taap.2018.06.012_bb0160","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1023\/A:1016351330832","article-title":"Effect of uridine on the metabolism of 5-fluorouracil in the CD8F 1 murine mammary carcinoma system","volume":"1","author":"Sawyer","year":"1984","journal-title":"Pharm. Res."},{"key":"10.1016\/j.taap.2018.06.012_bb0165","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/BF00543978","article-title":"Nonlinear pharmacokinetic characteristics of 5-fluorouracil (5-FU) in colorectal cancer patients","volume":"32","author":"Schaaf","year":"1987","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"10.1016\/j.taap.2018.06.012_bb0170","first-page":"6956","article-title":"Pharmacokinetics of 5-fluorouracil assessed with a sensitive mass spectrometric method in patients on a dose escalation schedule","volume":"48","author":"van Groeningen","year":"1988","journal-title":"Cancer Res."},{"key":"10.1016\/j.taap.2018.06.012_bb0175","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1093\/jnci\/83.6.437","article-title":"Clinical and pharmacologic study of orally administered uridine","volume":"83","author":"van Groeningen","year":"1991","journal-title":"J. Natl. Cancer Inst."},{"key":"10.1016\/j.taap.2018.06.012_bb0180","first-page":"1149","article-title":"Lethal outcome of a patient with a complete dihydropyrimidine dehydrogenase (DPD) deficiency after administration of 5-fluorouracil: frequency of the common IVS14+1G>A mutation causing DPD deficiency","volume":"7","author":"van Kuilenburg","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.taap.2018.06.012_bb0185","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/annonc\/mdg056","article-title":"Lethal 5-fluorouracil toxicity associated with a novel mutation in the dihydropyrimidine dehydrogenase gene","volume":"14","author":"van Kuilenburg","year":"2003","journal-title":"Ann. Oncol."},{"issue":"11","key":"10.1016\/j.taap.2018.06.012_bb0190","doi-asserted-by":"crossref","first-page":"e178","DOI":"10.1002\/phar.1841","article-title":"Early onset 5-fluorouracil toxicity in a patient negative for dihydropyrimidine dehydrogenase mutations: the clinical course of reversal with uridine triacetate","volume":"36","author":"Vaudo","year":"2016","journal-title":"Pharmacotherapy"},{"key":"10.1016\/j.taap.2018.06.012_bb0195","doi-asserted-by":"crossref","first-page":"e19562","DOI":"10.1200\/jco.2011.29.15_suppl.e19562","article-title":"Point-of-care (POC) diagnostic assay for 5-fluorouracil (5-FU) quantitation to enable dose adjustment and detect dihydropyrimidine dehydrogenase (DPD) deficiency","volume":"29","author":"White","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.taap.2018.06.012_bb0200","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/bjc.1997.79","article-title":"High-dose 5-fluorouracil infusional therapy is associated with hyperammonaemia, lactic acidosis and encephalopathy","volume":"75","author":"Yeh","year":"1997","journal-title":"Br. J. Cancer"}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X18302709?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X18302709?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T13:37:26Z","timestamp":1720359446000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X18302709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8]]},"references-count":40,"alternative-id":["S0041008X18302709"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2018.06.012","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2018,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Prompt treatment with uridine triacetate improves survival and reduces toxicity due to fluorouracil and capecitabine overdose or dihydropyrimidine dehydrogenase deficiency","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2018.06.012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}