{"id":"https://openalex.org/W2338213887","doi":"https://doi.org/10.1056/nejm197709222971203","title":"Use of Plasma Pharmacokinetics to Predict and Prevent Methotrexate Toxicity","display_name":"Use of Plasma Pharmacokinetics to Predict and Prevent Methotrexate Toxicity","publication_year":1977,"publication_date":"1977-09-22","ids":{"openalex":"https://openalex.org/W2338213887","doi":"https://doi.org/10.1056/nejm197709222971203","mag":"2338213887","pmid":"https://pubmed.ncbi.nlm.nih.gov/302412"},"language":"en","primary_location":{"id":"doi:10.1056/nejm197709222971203","doi":"https://doi.org/10.1056/nejm197709222971203","is_oa":false,"landing_page_url":"https://doi.org/10.1056/nejm197709222971203","pdf_url":null,"source":{"id":"https://openalex.org/S62468778","display_name":"New England Journal of Medicine","issn_l":"0028-4793","issn":["0028-4793","0096-6762","1533-4406","2331-4710"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320239","host_organization_name":"Massachusetts Medical Society","host_organization_lineage":["https://openalex.org/P4310320239"],"host_organization_lineage_names":["Massachusetts Medical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"New England Journal of Medicine","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5050436274","display_name":"Ronald G. Stoller","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ronald G. Stoller","raw_affiliation_strings":["Clinical Pharmacology, Surgery and Medicine branches of the National Cancer Institute, National Institutes of Health (address reprint requests to Dr. Chabner at Rm. 6N\u2013119, Bldg. 10, National Institutes of Health, Bethesda, MD 20014)"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Pharmacology, Surgery and Medicine branches of the National Cancer Institute, National Institutes of Health (address reprint requests to Dr. Chabner at Rm. 6N\u2013119, Bldg. 10, National Institutes of Health, Bethesda, MD 20014)","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5114031482","display_name":"Kenneth R. Hande","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kenneth R. Hande","raw_affiliation_strings":["Clinical Pharmacology, Surgery and Medicine branches of the National Cancer Institute, National Institutes of Health (address reprint requests to Dr. Chabner at Rm. 6N\u2013119, Bldg. 10, National Institutes of Health, Bethesda, MD 20014)"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Pharmacology, Surgery and Medicine branches of the National Cancer Institute, National Institutes of Health (address reprint requests to Dr. Chabner at Rm. 6N\u2013119, Bldg. 10, National Institutes of Health, Bethesda, MD 20014)","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112516366","display_name":"Samuel A. Jacobs","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Samuel A. Jacobs","raw_affiliation_strings":["Clinical Pharmacology, Surgery and Medicine branches of the National Cancer Institute, National Institutes of Health (address reprint requests to Dr. Chabner at Rm. 6N\u2013119, Bldg. 10, National Institutes of Health, Bethesda, MD 20014)"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Pharmacology, Surgery and Medicine branches of the National Cancer Institute, National Institutes of Health (address reprint requests to Dr. Chabner at Rm. 6N\u2013119, Bldg. 10, National Institutes of Health, Bethesda, MD 20014)","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5072133376","display_name":"Steven A. Rosenberg","orcid":"https://orcid.org/0000-0002-8939-8910","observed_orcids":["https://orcid.org/0000-0002-8939-8910"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Steven A. Rosenberg","raw_affiliation_strings":["Clinical Pharmacology, Surgery and Medicine branches of the National Cancer Institute, National Institutes of Health (address reprint requests to Dr. Chabner at Rm. 6N\u2013119, Bldg. 10, National Institutes of Health, Bethesda, MD 20014)"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Pharmacology, Surgery and Medicine branches of the National Cancer Institute, National Institutes of Health (address reprint requests to Dr. Chabner at Rm. 6N\u2013119, Bldg. 10, National Institutes of Health, Bethesda, MD 20014)","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5016346099","display_name":"Bruce Allan Chabner","orcid":"https://orcid.org/0000-0002-6306-2802","observed_orcids":["https://orcid.org/0000-0002-6306-2802"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Bruce A. Chabner","raw_affiliation_strings":["Clinical Pharmacology, Surgery and Medicine branches of the National Cancer Institute, National Institutes of Health (address reprint requests to Dr. Chabner at Rm. 6N\u2013119, Bldg. 10, National Institutes of Health, Bethesda, MD 20014)"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Pharmacology, Surgery and Medicine branches of the National Cancer Institute, National Institutes of Health (address reprint requests to Dr. Chabner at Rm. 6N\u2013119, Bldg. 10, National Institutes of Health, Bethesda, MD 20014)","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":15.0347,"has_fulltext":false,"cited_by_count":401,"citation_normalized_percentile":{"value":0.9965672,"is_in_top_1_percent":true,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":97,"max":100},"biblio":{"volume":"297","issue":"12","first_page":"630","last_page":"634"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.15489999949932098,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.15489999949932098,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12429","display_name":"Chemotherapy-induced organ toxicity mitigation","score":0.13009999692440033,"subfield":{"id":"https://openalex.org/subfields/2734","display_name":"Pathology and Forensic Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11845","display_name":"Cancer therapeutics and mechanisms","score":0.06469999998807907,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/methotrexate","display_name":"methotrexate","score":0.9850000143051147},{"id":"https://openalex.org/keywords/plasma-pharmacokinetics","display_name":"plasma pharmacokinetics","score":0.9089999794960022},{"id":"https://openalex.org/keywords/drug-toxicity-prediction","display_name":"drug toxicity prediction","score":0.7099999785423279},{"id":"https://openalex.org/keywords/myelosuppression","display_name":"myelosuppression","score":0.9850000143051147},{"id":"https://openalex.org/keywords/drug-clearance","display_name":"drug clearance","score":0.6629999876022339},{"id":"https://openalex.org/keywords/leucovorin-rescue","display_name":"leucovorin rescue","score":0.9639999866485596},{"id":"https://openalex.org/keywords/toxicity-prevention","display_name":"toxicity prevention","score":0.6269999742507935},{"id":"https://openalex.org/keywords/plasma-drug-concentration","display_name":"plasma drug concentration","score":0.5630000233650208}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.8816754221916199},{"id":"https://openalex.org/C2781059491","wikidata":"https://www.wikidata.org/wiki/Q422232","display_name":"Methotrexate","level":2,"score":0.8569766283035278},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.7982542514801025},{"id":"https://openalex.org/C29730261","wikidata":"https://www.wikidata.org/wiki/Q274160","display_name":"Toxicity","level":2,"score":0.7731938362121582},{"id":"https://openalex.org/C2911027401","wikidata":"https://www.wikidata.org/wiki/Q640448","display_name":"Intravenous Infusions","level":2,"score":0.6828489303588867},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.49282243847846985},{"id":"https://openalex.org/C2778397455","wikidata":"https://www.wikidata.org/wiki/Q50429865","display_name":"Antimetabolite","level":3,"score":0.47533321380615234},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.46797874569892883},{"id":"https://openalex.org/C19831878","wikidata":"https://www.wikidata.org/wiki/Q659446","display_name":"Therapeutic index","level":3,"score":0.4209928810596466},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3454620838165283},{"id":"https://openalex.org/C42219234","wikidata":"https://www.wikidata.org/wiki/Q131130","display_name":"Anesthesia","level":1,"score":0.3305988907814026}],"mesh":[{"descriptor_ui":"D001772","descriptor_name":"Blood Cell Count","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001792","descriptor_name":"Blood Platelets","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001853","descriptor_name":"Bone Marrow","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D002955","descriptor_name":"Leucovorin","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D002955","descriptor_name":"Leucovorin","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D003404","descriptor_name":"Creatinine","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007263","descriptor_name":"Infusions, Parenteral","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007668","descriptor_name":"Kidney","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D007958","descriptor_name":"Leukocyte Count","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008727","descriptor_name":"Methotrexate","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D008727","descriptor_name":"Methotrexate","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":false},{"descriptor_ui":"D008727","descriptor_name":"Methotrexate","qualifier_ui":"Q000633","qualifier_name":"toxicity","is_major_topic":true},{"descriptor_ui":"D009369","descriptor_name":"Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1056/nejm197709222971203","doi":"https://doi.org/10.1056/nejm197709222971203","is_oa":false,"landing_page_url":"https://doi.org/10.1056/nejm197709222971203","pdf_url":null,"source":{"id":"https://openalex.org/S62468778","display_name":"New England Journal of Medicine","issn_l":"0028-4793","issn":["0028-4793","0096-6762","1533-4406","2331-4710"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320239","host_organization_name":"Massachusetts Medical Society","host_organization_lineage":["https://openalex.org/P4310320239"],"host_organization_lineage_names":["Massachusetts Medical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"New England Journal of Medicine","raw_type":"journal-article"},{"id":"pmid:302412","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/302412","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The New England journal of medicine","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9940000176429749,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"score":0.800000011920929,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[{"display_name":"Observational Study","id":"https://openalex.org/study-designs/observational-study"}],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":9,"referenced_works":["https://openalex.org/W1563739340","https://openalex.org/W1974907966","https://openalex.org/W1976734173","https://openalex.org/W1992673437","https://openalex.org/W2011847171","https://openalex.org/W2080948320","https://openalex.org/W2082910236","https://openalex.org/W2130156939","https://openalex.org/W2317833459"],"related_works":["https://openalex.org/W2012653512","https://openalex.org/W2145662106","https://openalex.org/W2082017113","https://openalex.org/W2156153546","https://openalex.org/W49121034","https://openalex.org/W2370939713","https://openalex.org/W2973243615","https://openalex.org/W2416864229","https://openalex.org/W1899827437","https://openalex.org/W2430884327"],"abstract_inverted_index":{"To":[0],"correlate":[1],"the":[2,10,37,50,98,110],"pharmacokinetics":[3],"and":[4,42],"toxicity":[5,101],"of":[6,36,68,74,100,109,113,120,134,145],"methotrexate,":[7],"we":[8],"measured":[9],"drug's":[11],"clearance":[12,108],"from":[13,152],"plasma":[14,138],"after":[15,60,66],"395":[16],"high-dose,":[17],"six-hour":[18],"infusions":[19,76],"given":[20],"to":[21,105,124],"78":[22],"patients.":[23],"After":[24],"375":[25],"infusions,":[26,41,71],"48":[27],"hour":[28],"methotrexate":[29,135],"levels":[30],"fell":[31],"within":[32],"2":[33,57],"standard":[34,58],"deviations":[35],"mean":[38],"for":[39,52],"nontoxic":[40,53],"myelosuppression":[43,64],"did":[44],"not":[45],"occur.":[46],"Methotrexate":[47],"concentrations":[48,81,92],"exceeded":[49],"range":[51],"patients":[54,89,115,141],"(mean":[55],"+/-":[56],"deviations)":[59],"20":[61,70],"infusions.":[62],"Serious":[63],"occurred":[65],"six":[67,131],"these":[69,114],"including":[72],"five":[73],"12":[75],"associated":[77],"with":[78,90],"48-hour":[79,91],"drug":[80],"above":[82,93],"9":[83,94],"X":[84,95],"10(-7)":[85,96],"M.":[86],"In":[87],"seven":[88],"M,":[97],"absence":[99],"could":[102],"be":[103],"attributed":[104],"subsequent":[106],"rapid":[107],"drug;":[111],"four":[112],"also":[116],"received":[117],"large":[118],"doses":[119],"supplemental":[121,153],"leucovorin":[122,154],"(50":[123],"100":[125],"mg":[126],"per":[127],"square":[128],"meter":[129],"every":[130],"hours).":[132],"Determination":[133],"concentration":[136],"in":[137],"thus":[139],"identified":[140],"at":[142],"high":[143],"risk":[144],"toxicity,":[146],"a":[147],"group":[148],"that":[149],"may":[150],"benefit":[151],"rescue.":[155]},"counts_by_year":[{"year":2026,"cited_by_count":8},{"year":2025,"cited_by_count":7},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":8},{"year":2022,"cited_by_count":12},{"year":2021,"cited_by_count":12},{"year":2020,"cited_by_count":13},{"year":2019,"cited_by_count":10},{"year":2018,"cited_by_count":9},{"year":2017,"cited_by_count":14},{"year":2016,"cited_by_count":7},{"year":2015,"cited_by_count":6},{"year":2014,"cited_by_count":6},{"year":2013,"cited_by_count":6},{"year":2012,"cited_by_count":10}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}