{"id":"https://openalex.org/W2735618937","doi":"https://doi.org/10.1182/blood.v128.22.3652.3652","title":"Individualized Dosing of Hydroxyurea for Children with Sickle Cell Anemia Using a Population Pharmacokinetic-Based Model: The TREAT Study","display_name":"Individualized Dosing of Hydroxyurea for Children with Sickle Cell Anemia Using a Population Pharmacokinetic-Based Model: The TREAT Study","publication_year":2016,"publication_date":"2016-12-02","ids":{"openalex":"https://openalex.org/W2735618937","doi":"https://doi.org/10.1182/blood.v128.22.3652.3652","mag":"2735618937"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v128.22.3652.3652","doi":"https://doi.org/10.1182/blood.v128.22.3652.3652","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v128.22.3652.3652","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["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/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"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/A5017286562","display_name":"Patrick T. McGann","orcid":"https://orcid.org/0000-0001-6198-4785","observed_orcids":["https://orcid.org/0000-0001-6198-4785"]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Patrick T. McGann","raw_affiliation_strings":["Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5090500677","display_name":"Min Dong","orcid":"https://orcid.org/0000-0002-8552-8298","observed_orcids":["https://orcid.org/0000-0002-8552-8298"]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Min Dong","raw_affiliation_strings":["Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081533913","display_name":"Anu Marahatta","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Anu Marahatta","raw_affiliation_strings":["Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082637572","display_name":"Thad A. Howard","orcid":"https://orcid.org/0000-0002-9257-6343","observed_orcids":["https://orcid.org/0000-0002-9257-6343"]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Thad A. Howard","raw_affiliation_strings":["Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5016058238","display_name":"Tomoyuki Mizuno","orcid":"https://orcid.org/0000-0002-8471-9826","observed_orcids":["https://orcid.org/0000-0002-8471-9826"]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Tomoyuki Mizuno","raw_affiliation_strings":["Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020276338","display_name":"Karen Ann Kalinyak","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Karen A. Kalinyak","raw_affiliation_strings":["Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022133503","display_name":"Theodosia A. Kalfa","orcid":"https://orcid.org/0000-0002-0426-9686","observed_orcids":["https://orcid.org/0000-0002-0426-9686"]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Theodosia A. Kalfa","raw_affiliation_strings":["Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]},{"raw_affiliation_string":"Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5067822812","display_name":"Punam Malik","orcid":"https://orcid.org/0000-0002-8942-2108","observed_orcids":["https://orcid.org/0000-0002-8942-2108"]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Punam Malik","raw_affiliation_strings":["Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5065976686","display_name":"Omar Niss","orcid":"https://orcid.org/0000-0003-4157-4644","observed_orcids":["https://orcid.org/0000-0003-4157-4644"]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Omar Niss","raw_affiliation_strings":["Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5058382205","display_name":"Charles T. Quinn","orcid":"https://orcid.org/0000-0002-2372-2175","observed_orcids":["https://orcid.org/0000-0002-2372-2175"]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Charles T Quinn","raw_affiliation_strings":["Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040752648","display_name":"Russell E. Ware","orcid":"https://orcid.org/0000-0001-9582-0594","observed_orcids":["https://orcid.org/0000-0001-9582-0594"]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Russell E. Ware","raw_affiliation_strings":["Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5040060343","display_name":"Alexander A. T. M. M. Vinks","orcid":"https://orcid.org/0000-0003-4224-2967","observed_orcids":["https://orcid.org/0000-0003-4224-2967"]},"institutions":[{"id":"https://openalex.org/I1285204247","display_name":"Cincinnati Children's Hospital Medical Center","ror":"https://ror.org/01hcyya48","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1285204247"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Alexander A. Vinks","raw_affiliation_strings":["Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH","institution_ids":["https://openalex.org/I1285204247"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5016058238","https://openalex.org/A5020276338","https://openalex.org/A5040060343","https://openalex.org/A5081533913","https://openalex.org/A5082637572","https://openalex.org/A5090500677"],"corresponding_institution_ids":["https://openalex.org/I1285204247"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.7356,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":{"value":0.7744951,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":94},"biblio":{"volume":"128","issue":"22","first_page":"3652","last_page":"3652"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12547","display_name":"Pharmaceutical studies and practices","score":0.6128000020980835,"subfield":{"id":"https://openalex.org/subfields/2735","display_name":"Pediatrics, Perinatology and Child Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T12547","display_name":"Pharmaceutical studies and practices","score":0.6128000020980835,"subfield":{"id":"https://openalex.org/subfields/2735","display_name":"Pediatrics, Perinatology and Child Health"},"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/T10554","display_name":"Hemoglobinopathies and Related Disorders","score":0.3716000020503998,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics (clinical)"},"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/T11036","display_name":"Antibiotics Pharmacokinetics and Efficacy","score":0.002099999925121665,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/hydroxyurea","display_name":"hydroxyurea","score":0.9980000257492065},{"id":"https://openalex.org/keywords/sickle-cell-disease","display_name":"sickle cell disease","score":0.9959999918937683},{"id":"https://openalex.org/keywords/pediatric-patients","display_name":"pediatric patients","score":0.699999988079071},{"id":"https://openalex.org/keywords/individualized-dosing","display_name":"individualized dosing","score":0.9580000042915344},{"id":"https://openalex.org/keywords/population-pharmacokinetic-model","display_name":"population pharmacokinetic model","score":0.8199999928474426},{"id":"https://openalex.org/keywords/maximum-tolerated-dose","display_name":"maximum tolerated dose","score":0.8980000019073486},{"id":"https://openalex.org/keywords/sparse-sampling","display_name":"sparse sampling","score":0.6669999957084656},{"id":"https://openalex.org/keywords/therapeutic-drug-monitoring","display_name":"therapeutic drug monitoring","score":0.9459999799728394},{"id":"https://openalex.org/keywords/bayesian-estimation","display_name":"Bayesian estimation","score":0.6800000071525574},{"id":"https://openalex.org/keywords/area-under-the-curve","display_name":"area under the curve","score":0.7649999856948853},{"id":"https://openalex.org/keywords/dose-escalation","display_name":"dose escalation","score":0.48500001430511475},{"id":"https://openalex.org/keywords/treatment-response","display_name":"treatment response","score":0.3779999911785126}],"concepts":[{"id":"https://openalex.org/C2777288759","wikidata":"https://www.wikidata.org/wiki/Q4164182","display_name":"Dosing","level":2,"score":0.8170745372772217},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.7968420386314392},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.6251904964447021},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.6163138151168823},{"id":"https://openalex.org/C2779316324","wikidata":"https://www.wikidata.org/wiki/Q212272","display_name":"Hydroxycarbamide","level":3,"score":0.5267892479896545},{"id":"https://openalex.org/C2988731192","wikidata":"https://www.wikidata.org/wiki/Q7410159","display_name":"Blood sampling","level":2,"score":0.49363601207733154},{"id":"https://openalex.org/C2778248108","wikidata":"https://www.wikidata.org/wiki/Q5445","display_name":"Anemia","level":2,"score":0.49252328276634216},{"id":"https://openalex.org/C2778620579","wikidata":"https://www.wikidata.org/wiki/Q185034","display_name":"Sickle cell anemia","level":3,"score":0.45131778717041016},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3808450698852539},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.32676970958709717},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.16928204894065857},{"id":"https://openalex.org/C99454951","wikidata":"https://www.wikidata.org/wiki/Q932068","display_name":"Environmental health","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v128.22.3652.3652","doi":"https://doi.org/10.1182/blood.v128.22.3652.3652","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v128.22.3652.3652","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["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/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":1.0,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[{"display_name":"Clinical Trial","id":"https://openalex.org/study-designs/clinical-trial"}],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2533000830","https://openalex.org/W4310161270","https://openalex.org/W2172684893","https://openalex.org/W4405043834","https://openalex.org/W2533785708","https://openalex.org/W2913883561","https://openalex.org/W2944852231","https://openalex.org/W2913874492","https://openalex.org/W3082058144","https://openalex.org/W4405043441"],"abstract_inverted_index":{"Abstract":[0],"Background:":[1],"Hydroxyurea":[2,583],"is":[3,115,128,249,279,318,325,572,614],"the":[4,24,29,54,69,206,230,242,263,266,271,290,332,359,368,409,422,459,504,509,627,653],"primary":[5,126,316],"disease":[6],"modifying":[7],"therapy":[8],"for":[9,121,296,340,358,421,427,453,521,524],"patients":[10,73,527],"with":[11,74,88,123,159,234,433,444,451,581,591,630],"sickle":[12],"cell":[13],"anemia":[14],"(SCA).":[15],"The":[16,34,105,125,161,315,416],"clinical":[17,511,661],"and":[18,43,91,109,131,190,197,237,338,378,479,483,492,544,550,605,651,659],"laboratory":[19,635],"benefits":[20],"of":[21,36,77,99,119,175,178,227,285,300,367,383,413,440,466,501,623,640],"hydroxyurea":[22,66,102,120,139,217,238,247,357,411,452,577,624,649],"are":[23,200,210,219],"greatest":[25],"when":[26],"escalated":[27],"to":[28,39,51,53,62,96,129,137,152,281,319,327,330,334,380,534,547,574,617,656],"maximum":[30,335],"tolerated":[31],"dose":[32,37,171,277,323,341,401,412,507,512,518,531,542,622],"(MTD).":[33],"process":[35],"escalation":[38,532],"MTD":[40,70,140,295,658],"requires":[41],"expertise":[42],"can":[44],"be":[45],"tedious,":[46],"often":[47],"taking":[48,355,356],"6-12":[49],"months":[50,465,515,639],"titrate":[52],"optimal":[55],"dose.":[56],"In":[57,499],"addition,":[58],"due":[59,533,546],"in":[60,65,86,364,392,472,485,579,634],"part":[61],"inter-patient":[63],"variability":[64],"pharmacokinetics":[67],"(PK),":[68],"varies":[71],"among":[72],"a":[75,82,92,116,133,166,275,297,303,321,398,428,529,541,552,560,602,619],"range":[76],"15-35":[78],"mg/kg/day.":[79,415],"We":[80],"utilized":[81],"population":[83,134,231,611],"PK":[84,232,375,607,612],"model":[85,136,233,613],"combination":[87],"Bayesian":[89,235],"estimation":[90,236],"sparse":[93,147,561,593],"sampling":[94,148,155,162,393,562,594,608],"strategy,":[95],"individualize":[97],"dosing":[98,144,447,645,650],"children":[100,122,158,301,354,443,468,580],"starting":[101,276,322,431,461,621],"treatment.":[103],"Methods:":[104],"Therapeutic":[106],"Response":[107],"Evaluation":[108],"Adherence":[110],"Trial":[111],"(TREAT,":[112],"ClinicalTrials.gov":[113],"NCT02286154)":[114],"prospective":[117],"study":[118,305,424],"SCA.":[124,160,582],"objective":[127,317],"develop":[130],"evaluate":[132],"PK-based":[135,386,445],"predict":[138,618],"through":[141,350],"an":[142,224,283,384],"individualized":[143,385,643],"strategy.":[145],"A":[146],"approach":[149,595],"was":[150,289,589],"developed":[151],"allow":[153,381],"practical":[154],"from":[156,302],"young":[157,430,460],"strategy":[163],"includes":[164],"administering":[165],"single":[167,530],"oral":[168],"20":[169,353,369,414],"mg/kg":[170],"followed":[172],"by":[173,203,212,270,587],"collection":[174],"small":[176],"quantities":[177],"blood":[179,567],"(~100uL)":[180],"at":[181,241,294,408,454,513],"three":[182,243],"post-dosing":[183],"time":[184,245,333,361,654],"points":[185],"(15-20":[186],"minutes,":[187,189],"50-60":[188],"~3":[191],"hours).":[192],"Baseline":[193],"labs":[194],"(including":[195],"liver":[196],"renal":[198],"function)":[199],"typically":[201],"collected":[202,377],"venipuncture,":[204],"while":[205,388,538],"other":[207],"two":[208,438],"samples":[209,376,568],"drawn":[211],"fingerstick":[213],"or":[214,394],"heelstick.":[215],"Plasma":[216],"concentrations":[218,239],"measured":[220,240],"using":[221,223,251],"HPLC":[222],"internal":[225],"standard":[226,410,604],"methylurea.":[228],"Using":[229,262],"specified":[244],"points,":[246],"exposure":[248,578],"estimated":[250,269],"specialized":[252],"therapeutic":[253,336],"drug":[254],"monitoring":[255],"software":[256],"(MWPharm,":[257],"Mediware,":[258],"Prague,":[259],"Czech":[260],"Republic).":[261],"area":[264],"under":[265],"curve":[267],"(AUC0-inf)":[268],"model,":[272],"we":[273],"calculate":[274],"that":[278,324,396,559,599,625],"predicted":[280],"achieve":[282],"AUC":[284,292],"115":[286],"ug*h/mL,":[287],"which":[288],"mean":[291],"value":[293],"large":[298],"cohort":[299],"previous":[304,597],"(Dong":[306],"M":[307],"et":[308],"al.":[309],"Br":[310],"J":[311],"Clin":[312],"Pharmacol":[313],"2016).":[314],"select":[320],"close":[326],"actual":[328,628],"MTD,":[329,629],"reduce":[331,652],"effect":[337],"need":[339],"modifications":[342],"before":[343],"achieving":[344],"MTD.":[345],"Results:":[346],"From":[347],"December":[348],"2014":[349],"June":[351],"2016,":[352],"first":[360],"were":[362,406],"enrolled":[363],"TREAT.":[365],"Seventeen":[366],"participants":[370,405],"had":[371,390],"all":[372],"3":[373,389,404,566,570],"post-treatment":[374],"processed":[379],"calculation":[382],"dose,":[387],"difficulties":[391],"processing":[395],"prevented":[397],"safe":[399,620],"PK-guided":[400,505,644],"recommendation.":[402],"These":[403,556],"started":[407],"Table":[417,663],"summarizes":[418],"baseline":[419],"characteristics":[420],"initial":[423,446,506],"population,":[425],"notable":[426],"very":[429],"age":[432],"13/20":[434],"(65%)":[435],"less":[436],"than":[437],"years":[439],"age.":[441],"Twelve":[442],"have":[448,469],"been":[449],"treated":[450],"least":[455],"six":[456,464,514,638],"months.":[457],"Despite":[458],"age,":[462],"after":[463],"hydroxyurea,":[467],"documented":[470],"increases":[471],"total":[473],"Hb":[474],"(1.4+/-1.9":[475],"g/dL),":[476],"HbF":[477],"(11.3+/-6.4%),":[478],"MCV":[480],"(15+/-8":[481],"fL)":[482],"decreases":[484],"absolute":[486,493],"reticulocyte":[487],"count":[488,495],"(-217+/-128":[489],"x":[490,497],"109/L)":[491],"neutrophil":[494],"(-1.0+/-1.9":[496],"109/L).":[498],"9":[500],"12":[502],"participants,":[503],"remained":[508],"best":[510],"without":[516],"significant":[517,632],"changes":[519],"except":[520],"minor":[522],"adjustments":[523],"weight.":[525],"Two":[526],"required":[528,540],"inadequate":[535],"marrow":[536],"suppression,":[537],"one":[539],"hold":[543],"decrease":[545],"neutropenia":[548],"during":[549],"following":[551,637],"viral":[553],"infection.":[554],"Conclusions:":[555],"data":[557],"demonstrate":[558],"approach,":[563],"requiring":[564],"only":[565],"over":[569],"hours,":[571],"able":[573,616],"accurately":[575],"estimate":[576],"exposure,":[584],"as":[585,596],"defined":[586],"AUC,":[588],"similar":[590],"this":[592],"studies":[598],"relied":[600],"upon":[601],"more":[603],"prolonged":[606],"approach.":[609],"This":[610,642],"then":[615],"approximates":[626],"clinically":[631],"improvements":[633],"parameters":[636],"therapy.":[641],"regimen":[646],"should":[647],"simplify":[648],"interval":[655],"reach":[657],"maximal":[660],"benefits.":[662],"Table.":[664],"Disclosures":[665],"Kalfa:":[666],"Baxter/Baxalta/Shire:":[667],"Research":[668,672,676,680,686,696,701],"Funding.":[669,681,702],"Quinn:Silver":[670],"Lake":[671],"Corporation:":[673],"Consultancy;":[674,684,691,694],"Amgen:":[675],"Funding;":[677,687,697],"Eli":[678],"Lilly:":[679],"Ware:Nova":[682],"Laboratories:":[683],"Addmedica:":[685],"Global":[688],"Blood":[689],"Therapeutics:":[690],"Bayer":[692],"Pharmaceuticals:":[693],"Biomedomics:":[695],"Bristol":[698],"Myers":[699],"Squibb:":[700]},"counts_by_year":[{"year":2019,"cited_by_count":1},{"year":2018,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2017-07-21T00:00:00"}