{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:27:09Z","timestamp":1790011629947,"version":"4.0.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Chulalongkorn University Graduate Scholarship to Commemorate the 72nd Anniversary of His Majesty King Bhumibol Adulyadej"},{"name":"the 90th Anniversary of Chulalongkorn University Fund"},{"name":"the Thailand Science Research and Innovation Fund, Chulalongkorn University","award":["HEA663700098"],"award-info":[{"award-number":["HEA663700098"]}]},{"DOI":"10.13039\/501100020596","name":"Benoziyo Endowment Fund for the Advancement of Science","doi-asserted-by":"publisher","award":["[grant numbers CU_GR_63_58_37_05]"],"award-info":[{"award-number":["[grant numbers CU_GR_63_58_37_05]"]}],"id":[{"id":"10.13039\/501100020596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Introduction<\/jats:title>\n Irinotecan is a chemotherapy agent commonly prescribed for metastatic colorectal cancer but often leads to neutropenia. Variations in genes encoding drug-metabolizing enzymes and transporters may affect the toxicity and effectiveness of irinotecan. This study aimed to examine the impact of these genetic polymorphisms on irinotecan outcomes in Thai colorectal cancer patients.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The study retrospectively analyzed 41 metastatic colorectal cancer patients treated with irinotecan-based chemotherapy. Genotyping was conducted for 23 single nucleotide polymorphisms in genes including\n UGT1A1, CYP3A4, CYP3A5, CES1, ABCB1, ABCC2, ABCC5, ABCG1, ABCG2,<\/jats:italic>\n and\n SLCO1B1<\/jats:italic>\n .Toxicity and efficacy were assessed, with statistical significance set at a Bonferroni-corrected P value\u2009<\u20090.002.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In terms of toxicity,\n UGT1A1*6<\/jats:italic>\n was significantly associated with both all-grade and severe neutropenia in the first cycle (\n p<\/jats:italic>\n \u2009<\u20090.001) and severe neutropenia in the second cycle (\n p<\/jats:italic>\n \u2009<\u20090.002). Lower absolute neutrophil count was observed among intermediate and poor UGT1A1 metabolizers (\n p\u2009<\/jats:italic>\n <\u20090.001). The\n ABCC2<\/jats:italic>\n -24C\u2009>\u2009T variant was linked to all-grade neutropenia in the second cycle (\n p\u2009<\/jats:italic>\n =\u20090.001). For efficacy, patients with the wild-type\n UGT1A1*<\/jats:italic>\n 6 had longer progression-free survival (PFS) (\n p<\/jats:italic>\n \u2009<\u20090.002). Additionally, the\n SLCO1B1 521T\u2009>\u2009C<\/jats:italic>\n variant was associated with improved PFS (\n p<\/jats:italic>\n \u2009<\u20090.002).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n UGT1A1*6<\/jats:italic>\n and\n ABCC2<\/jats:italic>\n -24C\u2009>\u2009T variants emerge as potential predictors of irinotecan-induced neutropenia, while\n UGT1A1*6<\/jats:italic>\n and\n SLCO1B1 521T\u2009>\u2009C<\/jats:italic>\n may serve as markers of prolonged PFS in Thai patients. Validation through larger prospective studies is essential to confirm and refine these genetic associations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0338442","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:24:57Z","timestamp":1765563897000},"page":"e0338442","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impacts of polymorphisms in drug-metabolizing enzyme and transporter genes on irinotecan toxicity and efficacy in Thai colorectal cancer patients"],"prefix":"10.1371","volume":"20","author":[{"given":"Natthakul","family":"Akarapredee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chalirmporn","family":"Atasilp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chonlaphat","family":"Sukasem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pimonpan","family":"Jinda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rattanaporn","family":"Sukprasong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiraporn","family":"Jensuriyarkun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soravit","family":"Wongjitjanyong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patompong","family":"Satapornpong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2230-3593","authenticated-orcid":true,"given":"Natchaya","family":"Vanwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"issue":"9","key":"pone.0338442.ref001","doi-asserted-by":"crossref","first-page":"998","DOI":"10.2174\/18735592MTEx9NTk2y","article-title":"Colorectal cancer epidemiology: recent trends and impact on outcomes","volume":"22","author":"F Baidoun","year":"2021","journal-title":"Curr Drug Targets"},{"issue":"4","key":"pone.0338442.ref002","doi-asserted-by":"crossref","first-page":"499","DOI":"10.5946\/ce.2020.245-IDEN","article-title":"Current status of colorectal cancer and its public health burden in Thailand","volume":"54","author":"K Tiankanon","year":"2021","journal-title":"Clin Endosc"},{"issue":"1","key":"pone.0338442.ref003","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4103\/ijc.IJC_507_19","article-title":"Optimum patient selection for irinotecan-containing regimens in metastatic colorectal cancer: Literature review and lessons from clinical practice","volume":"58","author":"M Basade","year":"2021","journal-title":"Indian J Cancer"},{"issue":"2","key":"pone.0338442.ref004","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1177\/0300891618811283","article-title":"Irinotecan toxicity during treatment of metastatic colorectal cancer: focus on pharmacogenomics and personalized medicine","volume":"106","author":"A Paul\u00edk","year":"2020","journal-title":"Tumori"},{"issue":"10","key":"pone.0338442.ref005","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1007\/s40262-018-0644-7","article-title":"Individualization of irinotecan treatment: A review of pharmacokinetics, pharmacodynamics, and pharmacogenetics","volume":"57","author":"FM de Man","year":"2018","journal-title":"Clin Pharmacokinet"},{"issue":"9","key":"pone.0338442.ref006","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.2217\/pgs-2015-0006","article-title":"Efflux transporter variants as predictors of drug toxicity in lung cancer patients: systematic review and meta-analysis","volume":"17","author":"ZM Za\u00efr","year":"2016","journal-title":"Pharmacogenomics"},{"issue":"12","key":"pone.0338442.ref007","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/FPC.0000000000000168","article-title":"ABCC5 and ABCG1 polymorphisms predict irinotecan-induced severe toxicity in metastatic colorectal cancer patients","volume":"25","author":"S Chen","year":"2015","journal-title":"Pharmacogenet Genomics"},{"issue":"6","key":"pone.0338442.ref008","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.clpt.2004.01.010","article-title":"UGT1A1 haplotypes associated with reduced glucuronidation and increased serum bilirubin in irinotecan-administered Japanese patients with cancer","volume":"75","author":"K Sai","year":"2004","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"pone.0338442.ref009","doi-asserted-by":"crossref","first-page":"13486","DOI":"10.1038\/s41598-020-70351-0","article-title":"Effect of drug metabolizing enzymes and transporters in Thai colorectal cancer patients treated with irinotecan-based chemotherapy","volume":"10","author":"C Atasilp","year":"2020","journal-title":"Sci Rep"},{"issue":"9","key":"pone.0338442.ref010","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/s41431-022-01243-2","article-title":"Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan","volume":"31","author":"EC Hulshof","year":"2023","journal-title":"Eur J Hum Genet"},{"issue":"2","key":"pone.0338442.ref011","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s13318-021-00675-3","article-title":"Effect of UGT1A1, CYP3A and CES activities on the pharmacokinetics of irinotecan and its metabolites in patients with UGT1A1 gene polymorphisms","volume":"46","author":"A Yokokawa","year":"2021","journal-title":"Eur J Drug Metab Pharmacokinet"},{"issue":"4","key":"pone.0338442.ref012","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/86882","article-title":"Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression","volume":"27","author":"P Kuehl","year":"2001","journal-title":"Nat Genet"},{"issue":"4","key":"pone.0338442.ref013","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/em.10199","article-title":"Increased transcriptional activity of the CYP3A4*1B promoter variant","volume":"42","author":"B Amirimani","year":"2003","journal-title":"Environ Mol Mutagen"},{"issue":"11","key":"pone.0338442.ref014","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1007\/s40262-023-01279-7","article-title":"Irinotecan-Induced Toxicity: A Pharmacogenetic Study Beyond UGT1A1","volume":"62","author":"M de With","year":"2023","journal-title":"Clin Pharmacokinet"},{"issue":"9","key":"pone.0338442.ref015","first-page":"3246","article-title":"Irinotecan pathway genotype analysis to predict pharmacokinetics","volume":"9","author":"RHJ Mathijssen","year":"2003","journal-title":"Clin Cancer Res"},{"issue":"16","key":"pone.0338442.ref016","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1200\/JCO.2008.20.6300","article-title":"Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics","volume":"27","author":"F Innocenti","year":"2009","journal-title":"J Clin Oncol"},{"issue":"1","key":"pone.0338442.ref017","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/tpj.2010.10","article-title":"Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer","volume":"11","author":"B Glimelius","year":"2011","journal-title":"Pharmacogenomics J"},{"issue":"1","key":"pone.0338442.ref018","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.lungcan.2007.12.003","article-title":"Integrated pharmacogenetic prediction of irinotecan pharmacokinetics and toxicity in patients with advanced non-small cell lung cancer","volume":"63","author":"J-Y Han","year":"2009","journal-title":"Lung Cancer"},{"issue":"1","key":"pone.0338442.ref019","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/tpj.2015.23","article-title":"Clinical validity of new genetic biomarkers of irinotecan neutropenia: an independent replication study","volume":"16","author":"DJ Crona","year":"2016","journal-title":"Pharmacogenomics J"},{"issue":"5","key":"pone.0338442.ref020","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/bjc.2015.5","article-title":"OATP1B1 and tumour OATP1B3 modulate exposure, toxicity, and survival after irinotecan-based chemotherapy","volume":"112","author":"WA Teft","year":"2015","journal-title":"Br J Cancer"},{"issue":"2","key":"pone.0338442.ref021","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"EA Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"issue":"1","key":"pone.0338442.ref022","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00280-017-3344-3","article-title":"UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia: a systematic review and meta-analysis","volume":"80","author":"X Zhang","year":"2017","journal-title":"Cancer Chemother Pharmacol"},{"issue":"1","key":"pone.0338442.ref023","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.dmpk.2015.12.004","article-title":"Correlation of UGT1A1(*)28 and (*)6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients","volume":"31","author":"C Atasilp","year":"2016","journal-title":"Drug Metab Pharmacokinet"},{"key":"pone.0338442.ref024","first-page":"428","article-title":"Polymorphisms of uridine glucuronosyltransferase gene and irinotecan toxicity: low dose does not protect from toxicity","volume":"8","author":"M Tziotou","year":"2014","journal-title":"Ecancermedicalscience"},{"issue":"15","key":"pone.0338442.ref025","doi-asserted-by":"crossref","first-page":"5151","DOI":"10.1158\/1078-0432.CCR-03-0548","article-title":"Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study of 75 patients","volume":"10","author":"E Rouits","year":"2004","journal-title":"Clin Cancer Res"},{"issue":"1","key":"pone.0338442.ref026","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12876-020-01227-w","article-title":"Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer: a study from Guangxi Zhuang","volume":"20","author":"S Chen","year":"2020","journal-title":"BMC Gastroenterol"},{"issue":"4","key":"pone.0338442.ref027","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/cpt.269","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing","volume":"99","author":"RS Gammal","year":"2016","journal-title":"Clin Pharmacol Ther"},{"issue":"5","key":"pone.0338442.ref028","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1097\/00008571-199910000-00006","article-title":"Variability at the uridine diphosphate glucuronosyltransferase 1A1 promoter in human populations and primates","volume":"9","author":"D Hall","year":"1999","journal-title":"Pharmacogenetics"},{"issue":"14","key":"pone.0338442.ref029","doi-asserted-by":"crossref","first-page":"8170","DOI":"10.1073\/pnas.95.14.8170","article-title":"Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism?","volume":"95","author":"E Beutler","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pone.0338442.ref030","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00280-014-2382-3","article-title":"UGT1A1*6 polymorphisms are correlated with irinotecan-induced toxicity: a system review and meta-analysis in Asians","volume":"73","author":"L Cheng","year":"2014","journal-title":"Cancer Chemother Pharmacol"},{"issue":"1","key":"pone.0338442.ref031","first-page":"21","article-title":"Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese","volume":"46","author":"K Akaba","year":"1998","journal-title":"Biochem Mol Biol Int"},{"issue":"4","key":"pone.0338442.ref032","doi-asserted-by":"crossref","first-page":"691","DOI":"10.7150\/jca.17210","article-title":"Predictive value of UGT1A1*28 polymorphism in irinotecan-based chemotherapy","volume":"8","author":"XH Liu","year":"2017","journal-title":"J Cancer"},{"issue":"1","key":"pone.0338442.ref033","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00280-018-3595-7","article-title":"UGT1A polymorphisms associated with worse outcome in colorectal cancer patients treated with irinotecan-based chemotherapy","volume":"82","author":"Q Yu","year":"2018","journal-title":"Cancer Chemother Pharmacol"},{"issue":"1","key":"pone.0338442.ref034","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/tpj.2016.58","article-title":"Irinotecan-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses","volume":"17","author":"JM Campbell","year":"2017","journal-title":"Pharmacogenomics J"},{"issue":"5","key":"pone.0338442.ref035","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/tpj.2014.16","article-title":"The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy: a collaborative meta-analysis","volume":"14","author":"MM Dias","year":"2014","journal-title":"Pharmacogenomics J"},{"key":"pone.0338442.ref036","first-page":"1653","article-title":"Clinical significance of UGT1A1 gene polymorphisms on irinotecan-based regimens as the treatment in metastatic colorectal cancer","volume":"7","author":"M Li","year":"2014","journal-title":"Onco Targets Ther"},{"issue":"15","key":"pone.0338442.ref037","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1200\/JCO.2005.03.0239","article-title":"Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin","volume":"24","author":"J-Y Han","year":"2006","journal-title":"J Clin Oncol"},{"key":"pone.0338442.ref038","first-page":"728","article-title":"Associations of ABCB1, ABCC2, and ABCG2 polymorphisms with irinotecan-pharmacokinetics and clinical outcome in patients with advanced non-small cell lung cancer","volume":"67","author":"JY Han","year":"2007","journal-title":"Cancer Research"},{"issue":"1","key":"pone.0338442.ref039","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/sj.tpj.6500403","article-title":"Influence of polymorphisms of ABCB1 and ABCC2 on mRNA and protein expression in normal and cancerous kidney cortex","volume":"7","author":"S Haenisch","year":"2007","journal-title":"Pharmacogenomics J"},{"issue":"3","key":"pone.0338442.ref040","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2133\/dmpk.DMPK-11-RG-128","article-title":"Association of ABCC2 genotype with efficacy of first-line FOLFIRI in Japanese patients with advanced colorectal cancer","volume":"27","author":"Y Akiyama","year":"2012","journal-title":"Drug Metab Pharmacokinet"},{"issue":"1","key":"pone.0338442.ref041","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/sj.clpt.6100019","article-title":"Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2 transporter protein","volume":"81","author":"FA de Jong","year":"2007","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"pone.0338442.ref042","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/cncr.22760","article-title":"Associations of ABCB1, ABCC2, and ABCG2 polymorphisms with irinotecan-pharmacokinetics and clinical outcome in patients with advanced non-small cell lung cancer","volume":"110","author":"J-Y Han","year":"2007","journal-title":"Cancer"},{"issue":"11","key":"pone.0338442.ref043","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1248\/bpb.31.2137","article-title":"Association of ATP-binding cassette, sub-family C, number 2 (ABCC2) genotype with pharmacokinetics of irinotecan in Japanese patients with metastatic colorectal cancer treated with irinotecan plus infusional 5-fluorouracil\/leucovorin (FOLFIRI)","volume":"31","author":"K Fujita","year":"2008","journal-title":"Biol Pharm Bull"},{"issue":"10","key":"pone.0338442.ref044","first-page":"2757","article-title":"Effects of ABCC2 and SLCO1B1 Polymorphisms on Treatment Responses in Thai Metastatic Colorectal Cancer Patients Treated with Irinotecan-Based Chemotherapy","volume":"19","author":"A Treenert","year":"2018","journal-title":"Asian Pac J Cancer Prev"},{"issue":"10","key":"pone.0338442.ref045","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0077223","article-title":"SLCO1B1 and SLC19A1 gene variants and irinotecan-induced rapid response and survival: a prospective multicenter pharmacogenetics study of metastatic colorectal cancer","volume":"8","author":"L Huang","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"pone.0338442.ref046","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.lungcan.2007.07.019","article-title":"Influence of the organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphisms on irinotecan-pharmacokinetics and clinical outcome of patients with advanced non-small cell lung cancer","volume":"59","author":"J-Y Han","year":"2008","journal-title":"Lung Cancer"},{"issue":"9","key":"pone.0338442.ref047","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1097\/01.fpc.0000230420.05221.71","article-title":"Pharmacogenetics of SLCO1B1 gene and the impact of *1b and *15 haplotypes on irinotecan disposition in Asian cancer patients","volume":"16","author":"X Xiang","year":"2006","journal-title":"Pharmacogenet Genomics"},{"issue":"1","key":"pone.0338442.ref048","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1124\/pr.110.002857","article-title":"Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake","volume":"63","author":"M Niemi","year":"2011","journal-title":"Pharmacol Rev"},{"issue":"1","key":"pone.0338442.ref049","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gr.129668.111","article-title":"Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition","volume":"22","author":"LB Ramsey","year":"2012","journal-title":"Genome Res"},{"issue":"3","key":"pone.0338442.ref050","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00280-021-04314-1","article-title":"Minimal contribution of the hepatic uptake transporter OATP1B1 to the inter-individual variability in SN-38 pharmacokinetics in cancer patients without severe renal failure","volume":"88","author":"A Tsuboya","year":"2021","journal-title":"Cancer Chemother Pharmacol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0338442","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:25:07Z","timestamp":1765563907000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0338442"}},"subtitle":[],"editor":[{"given":"Germana","family":"Bancone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":50,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0338442","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]}}}