{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:33:27Z","timestamp":1791812007484,"version":"4.3.4"},"reference-count":44,"publisher":"Walter de Gruyter GmbH","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2025-0949_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the relationship between uracilemia (U)\u00a0and dihydropyrimidine dehydrogenase (DPD) activity in peripheral blood mononuclear cells (PBMC) and whether they are influenced by renal or hepatic impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0949_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study included 176 cancer patients with pre-treatment U (UPLC-MSMS assay) and PBMC-DPD (radioenzymatic assay) analyzed the same day (routine phenotyping). Blood renal (creatinine, BUN) and hepatic (ALT, AST, GGT, ALP, albumin, bilirubin) work-up was performed within 15\u00a0days before or up to 4\u00a0days after DPD phenotyping. Biochemical markers were categorized according to CTCAEv5.0 grade (G). Glomerular filtration rate (eGFR) was estimated (CKD-EPI and EKFC). Non-parametric statistical tests were\u00a0used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0949_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Prevalence of partial deficiency was 3.4\u202f% based on PBMC-DPD (i.e.\u00a0\u2264100\u202fpmol\/min\/mg) and 6.3\u202f% based on U (i.e.\u00a0\u226516\u202f\u03bcg\/L). No complete deficiency was observed. Fifteen patients out of 176 (8.5\u202f%) exhibited discordant DPD status between PBMC activity and U. The correlation between PBMC-DPD and U was significant but weak (r=\u00a0\u22120.309, p&lt;0.001). PBMC-DPD (mean 246, median 235, range 62\u2013926\u202fpmol\/min\/mg prot) was not influenced by renal or hepatic impairment. U (mean 9.6, median 8.5, range 1.7\u201357.8\u202f\u03bcg\/L) was significantly higher in patients with elevated BUN (normal vs. &gt;1-UNL, p=0.009), GGT (G0 vs. G1 vs. G2 vs. G3, p&lt;0.001), AST (G0 vs. G\u22651, p=0.015), or with hypoalbuminemia (G0 vs. G\u00a0\u2265\u00a01, p=0.045). Categorized creatinine or eGFR did not influence\u00a0U.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0949_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>It remains unclear whether renal and\/or hepatic impairment acts as a confounding factor affecting the accuracy of uracilemia testing, or whether truly impacts DPD activity, suggesting caution in U interpretation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2025-0949","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T13:22:53Z","timestamp":1758115373000},"page":"166-175","source":"Crossref","is-referenced-by-count":5,"title":["Impact of renal and hepatic function on dihydropyrimidine dehydrogenase phenotype assessed by enzyme activity in peripheral blood mononuclear cells and uracilemia"],"prefix":"10.1515","volume":"64","author":[{"given":"Sara","family":"Contu","sequence":"first","affiliation":[{"name":"Department of Epidemiology , 55121 Biostatistics and Health Data, Centre Antoine Lacassagne, University of C\u00f4te d\u2019Azur , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Launay","sequence":"additional","affiliation":[{"name":"Department of Pharmacology , Institut Curie, PSL Research University , Saint-Cloud , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Bouges Le Royer","sequence":"additional","affiliation":[{"name":"Oncopharmacology Department , Centre Antoine Lacassagne, University of C\u00f4te d\u2019Azur , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Simon","sequence":"additional","affiliation":[{"name":"Oncopharmacology Department , Centre Antoine Lacassagne, University of C\u00f4te d\u2019Azur , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Mignot","sequence":"additional","affiliation":[{"name":"Oncopharmacology Department , Centre Antoine Lacassagne, University of C\u00f4te d\u2019Azur , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Seutin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology , 55121 Biostatistics and Health Data, Centre Antoine Lacassagne, University of C\u00f4te d\u2019Azur , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Schiappa","sequence":"additional","affiliation":[{"name":"Department of Epidemiology , 55121 Biostatistics and Health Data, Centre Antoine Lacassagne, University of C\u00f4te d\u2019Azur , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Follana","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology , Centre Antoine Lacassagne , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Creisson","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department for Outpatient Care Pathway Coordination , Centre Antoine Lacassagne, University of C\u00f4te d\u2019Azur , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Evesque","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology , Centre Antoine Lacassagne , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Etienne-Grimaldi","sequence":"additional","affiliation":[{"name":"Oncopharmacology Department , Centre Antoine Lacassagne, University of C\u00f4te d\u2019Azur , Nice , France"},{"name":"Laboratory of Translational Research in Oncology (LRTO) , University of C\u00f4te d\u2019Azur , Nice , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"2025121815555029461_j_cclm-2025-0949_ref_001","doi-asserted-by":"crossref","unstructured":"Gmeiner, WH, Okechukwu, CC. Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects. Cancer Drug Resist 2023;6:257\u201372. https:\/\/doi.org\/10.20517\/cdr.2022.136.","DOI":"10.20517\/cdr.2022.136"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_002","doi-asserted-by":"crossref","unstructured":"Le Teuff, G, Cozic, N, Boyer, JC, Boige, V, Diasio, RB, Taieb, J, et al.. Dihydropyrimidine dehydrogenase gene variants for predicting grade 4\u20135\u00a0fluoropyrimidine-induced toxicity: FUSAFE individual patient data meta-analysis. Br J Cancer 2024;15.","DOI":"10.1038\/s41416-023-02517-2"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_003","unstructured":"Chazal, M, Etienne, MC, Ren\u00e9e, N, Bourgeon, A, Richelme, H, Milano, G. Link between dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells and liver. Clin Cancer Res 1996;2:507\u201310."},{"key":"2025121815555029461_j_cclm-2025-0949_ref_004","doi-asserted-by":"crossref","unstructured":"Loriot, MA, Ciccolini, J, Thomas, F, Barin-Le-Guellec, C, Royer, B, Milano, G, et al.. Dihydropyrimidine d\u00e9hydrogenase (DPD) deficiency screening and securing of fluoropyrimidine-based chemotherapies: update and recommendations of the French GPCO-Unicancer and RNPGx networks. Bull Cancer 2018;105:397\u2013407. https:\/\/doi.org\/10.1016\/j.bulcan.2018.02.001.","DOI":"10.1016\/j.bulcan.2018.02.001"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_005","doi-asserted-by":"crossref","unstructured":"Etienne-Grimaldi, MC, Pallet, N, Boige, V, Ciccolini, J, Chouchana, L, Barin-Le Guellec, C, et al.. Current diagnostic and clinical issues of screening for dihydropyrimidine dehydrogenase deficiency. Eur J Cancer 2023;181:3\u201317. https:\/\/doi.org\/10.1016\/j.ejca.2022.11.028.","DOI":"10.1016\/j.ejca.2022.11.028"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_006","doi-asserted-by":"crossref","unstructured":"van Kuilenburg, ABP, De Abreu, RA, van Gennip, AH. Pharmacogenetic and clinical aspects of dihydropyrimidine dehydrogenase deficiency. Ann Clin Biochem 2003;40:41\u20135. https:\/\/doi.org\/10.1258\/000456303321016150.","DOI":"10.1258\/000456303321016150"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_007","unstructured":"Fleming, RA, Milano, G, Thyss, A, Etienne, MC, Ren\u00e9e, N, Schneider, M, et al.. Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients. Cancer Res 1992;52:2899\u2013902."},{"key":"2025121815555029461_j_cclm-2025-0949_ref_008","doi-asserted-by":"crossref","unstructured":"Boisdron-Celle, M, Remaud, G, Traore, S, Poirier, AL, Gamelin, L, Morel, A, et al.. 5-Fluorouracil-related severe toxicity: a comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. Cancer Lett 2007;249:271\u201382. https:\/\/doi.org\/10.1016\/j.canlet.2006.09.006.","DOI":"10.1016\/j.canlet.2006.09.006"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_009","doi-asserted-by":"crossref","unstructured":"Caudle, KE, Thorn, CF, Klein, TE, Swen, JJ, McLeod, HL, Diasio, RB, et al.. Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther 2013;94:640\u20135. https:\/\/doi.org\/10.1038\/clpt.2013.172.","DOI":"10.1038\/clpt.2013.172"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_010","doi-asserted-by":"crossref","unstructured":"Pratt, VM. Updates to American medical association\u2019s current procedural terminology codes for oncology panel testing. J\u00a0Mol Diagn 2024;26:231\u20132, https:\/\/doi.org\/10.1016\/j.jmoldx.2024.01.002.","DOI":"10.1016\/j.jmoldx.2024.01.002"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_011","doi-asserted-by":"crossref","unstructured":"Royer, B, Launay, M, Ciccolini, J, Derain, L, Parant, F, Thomas, F, et al.. Impact of renal impairment on dihydropyrimidine dehydrogenase (DPD) phenotyping. ESMO Open 2023;8:101577. https:\/\/doi.org\/10.1016\/j.esmoop.2023.101577.","DOI":"10.1016\/j.esmoop.2023.101577"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_012","doi-asserted-by":"crossref","unstructured":"Callon, S, Brugel, M, Botsen, D, Royer, B, Slimano, F, Feliu, C, et al.. Renal impairment and abnormal liver function tests in pre-therapeutic phenotype-based DPD deficiency screening using uracilemia: a comprehensive population-based study in 1138 patients. Ther Adv Med Oncol 2023;15:17588359221148536. https:\/\/doi.org\/10.1177\/17588359221148536.","DOI":"10.1177\/17588359221148536"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_013","doi-asserted-by":"crossref","unstructured":"Gaible, C, Narjoz, C, Loriot, MA, Roueff, S, Pallet, N. Pretherapeutic screening for Dihydropyrimidine deshydrogenase deficiency in measuring uracilemia in dialysis patients leads to a high rate of falsely positive results. Cancer Chemother Pharmacol 2021;88:1049\u201353. https:\/\/doi.org\/10.1007\/s00280-021-04354-7.","DOI":"10.1007\/s00280-021-04354-7"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_014","doi-asserted-by":"crossref","unstructured":"Arriv\u00e9, C, Fonrose, X, Thomas, F, Roth, G, Jacquet, E, Brice, A, et al.. Discrepancies between dihydropyrimidine dehydrogenase phenotyping and genotyping: what are the explanatory factors? Br J Clin Pharmacol 2023;89:2446\u201357. https:\/\/doi.org\/10.1111\/bcp.15715.","DOI":"10.1111\/bcp.15715"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_015","doi-asserted-by":"crossref","unstructured":"Jacobs, BAW, Rosing, H, de Vries, N, Meulendijks, D, Henricks, LM, Schellens, JHM, et al.. Development and validation of a rapid and sensitive UPLC-MS\/MS method for determination of uracil and dihydrouracil in human plasma. J\u00a0Pharm Biomed Anal 2016;126:75\u201382. https:\/\/doi.org\/10.1016\/j.jpba.2016.04.039","DOI":"10.1016\/j.jpba.2016.04.039"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_016","unstructured":"Recherche de d\u00e9ficit en dihydropyrimidine d\u00e9shydrog\u00e9nase en vue de pr\u00e9venir certaines toxicit\u00e9s s\u00e9v\u00e8res survenant sous traitement comportant des fluoropyrimidines [Internet] 2018. Available from: https:\/\/www.has-sante.fr\/portail\/upload\/docs\/application\/pdf\/2018-12\/recherche_dun_deficit_en_dihydropyrimidine_deshydrogenase_visant_a_prevenir_certaines_toxicites_severes_associees_aux_traite.pdf."},{"key":"2025121815555029461_j_cclm-2025-0949_ref_017","unstructured":"Harris, BE, Song, R, Soong, SJ, Diasio, RB. Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion. Cancer Res 1990;50:197\u2013201."},{"key":"2025121815555029461_j_cclm-2025-0949_ref_018","doi-asserted-by":"crossref","unstructured":"Etienne, MC, Lagrange, JL, Dassonville, O, Fleming, R, Thyss, A, Ren\u00e9e, N, et al.. Population study of dihydropyrimidine dehydrogenase in cancer patients. J\u00a0Clin Oncol 1994;12:2248\u201353. https:\/\/doi.org\/10.1200\/jco.1994.12.11.2248.","DOI":"10.1200\/JCO.1994.12.11.2248"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_019","doi-asserted-by":"crossref","unstructured":"Burns, KE, Chavani, O, Jeong, SH, Duley, JA, Porter, D, Findlay, M, et al.. Comparison of a thymine challenge test and endogenous uracil-dihydrouracil levels for assessment of fluoropyrimidine toxicity risk. Cancer Chemother Pharmacol 2021;87:711\u20136. https:\/\/doi.org\/10.1007\/s00280-021-04240-2.","DOI":"10.1007\/s00280-021-04240-2"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_020","unstructured":"Common Terminology Criteria for Adverse Events (CTCAE) | protocol development | CTEP [Internet]. Available from: https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/ctc.htm#ctc_50 [Accessed 9 Apr 2025]."},{"key":"2025121815555029461_j_cclm-2025-0949_ref_021","doi-asserted-by":"crossref","unstructured":"Launay, M, Raymond, L, Guitton, J, Loriot, MA, Chatelut, E, Haufroid, V, et al.. Can we identify patients carrying targeted deleterious DPYD variants with plasma uracil and dihydrouracil? A GPCO-RNPGx retrospective analysis. Clin Chem Lab Med 2024;62:2415\u201324. https:\/\/doi.org\/10.1515\/cclm-2024-0317.","DOI":"10.1515\/cclm-2024-0317"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_022","doi-asserted-by":"crossref","unstructured":"Van Kuilenburg, AB, van Lenthe, H, Blom, MJ, Mul, EP, Van Gennip, AH. Profound variation in dihydropyrimidine dehydrogenase activity in human blood cells: major implications for the detection of partly deficient patients. Br J Cancer 1999;79:620\u20136. https:\/\/doi.org\/10.1038\/sj.bjc.6690097.","DOI":"10.1038\/sj.bjc.6690097"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_023","doi-asserted-by":"crossref","unstructured":"Etienne, MC, Chatelut, E, Pivot, X, Lavit, M, Pujol, A, Canal, P, et al.. Co-variables influencing 5-fluorouracil clearance during continuous venous infusion. A NONMEM analysis. Eur J Cancer 1998;34:92\u20137. https:\/\/doi.org\/10.1016\/s0959-8049-97-00345-6.","DOI":"10.1016\/S0959-8049(97)00345-6"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_024","doi-asserted-by":"crossref","unstructured":"Winther-Larsen, A, Madsen, AT, Nissen, PH, Hoffmann-L\u00fccke, E, Greibe, E. Short-term biological variation of plasma uracil in a Caucasian healthy population. Clin Chem Lab Med 2023;61:1490\u20136. https:\/\/doi.org\/10.1515\/cclm-2022-1167.","DOI":"10.1515\/cclm-2022-1167"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_025","doi-asserted-by":"crossref","unstructured":"Henricks, LM, Jacobs, BAW, Meulendijks, D, Pluim, D, van den Broek, D, de Vries, N, et al.. Food-effect study on uracil and dihydrouracil plasma levels as marker for dihydropyrimidine dehydrogenase activity in human volunteers. Br J Clin Pharmacol 2018;84:2761\u20139. https:\/\/doi.org\/10.1111\/bcp.13719.","DOI":"10.1111\/bcp.13719"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_026","doi-asserted-by":"crossref","unstructured":"Launay, M, Guitton, J, Balluet, R, Moreau, A, Phelip, JM, Tholance, Y, et al.. Clinical considerations for DPD deficiency testing in advanced cancer patients: tumor lysis syndrome should be considered as a major interference. Ann Oncol 2022;33:850\u20132. https:\/\/doi.org\/10.1016\/j.annonc.2022.04.073.","DOI":"10.1016\/j.annonc.2022.04.073"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_027","doi-asserted-by":"crossref","unstructured":"Ito, S, Kawamura, T, Inada, M, Inoue, Y, Hirao, Y, Koga, T, et al.. Physiologically based pharmacokinetic modelling of the three-step metabolism of pyrimidine using 13C-uracil as an in\u00a0vivo probe. Br J Clin Pharmacol 2005;60:584\u201393. https:\/\/doi.org\/10.1111\/j.1365-2125.2005.02472.x.","DOI":"10.1111\/j.1365-2125.2005.02472.x"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_028","doi-asserted-by":"crossref","unstructured":"Salvador, CL, Flemmen, PTK, T\u00f8ndel, C, Bliksrud, YT, Tsui, EFF, Brun, A, et al.. Renal function, sex and age influence purines and pyrimidines in urine and could lead to diagnostic misinterpretation. Mol Genet Metabol 2023;140:107649. https:\/\/doi.org\/10.1016\/j.ymgme.2023.107649.","DOI":"10.1016\/j.ymgme.2023.107649"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_029","doi-asserted-by":"crossref","unstructured":"Naylor, EW, Cederbaum, SD. Urinary pyrimidine excretion in arginase deficiency. J\u00a0Inherit Metab Dis 1981;4:207\u201310. https:\/\/doi.org\/10.1007\/bf02263653.","DOI":"10.1007\/BF02263653"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_030","doi-asserted-by":"crossref","unstructured":"Yeung, C, Shen, D, Thummel, K, Himmelfarb, J. Effects of chronic kidney disease and uremia on hepatic drug metabolism and transport. Kidney Int 2014;85:522\u20138.","DOI":"10.1038\/ki.2013.399"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_031","doi-asserted-by":"crossref","unstructured":"Nolin, TD, Naud, J, Leblond, FA, Pichette, V. Emerging evidence of the impact of kidney disease on drug metabolism and transport. Clin Pharmacol Ther 2008;83:898\u2013903. https:\/\/doi.org\/10.1038\/clpt.2008.59.","DOI":"10.1038\/clpt.2008.59"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_032","doi-asserted-by":"crossref","unstructured":"Matheux, A, Collas, L, Grisard, M, Goulaieff, L, Ghiringhelli, F, Bengrine-Lefevre, L, et al.. Plasma clearance of 5-fluorouracil is more influenced by variations in glomerular filtration rate than by uracil concentration. Cancer Chemother Pharmacol 2024;95:9. https:\/\/doi.org\/10.1007\/s00280-024-04732-x.","DOI":"10.1007\/s00280-024-04732-x"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_033","doi-asserted-by":"crossref","unstructured":"Makihara, K, Mishima, H, Azuma, S, Miyagi, K, Komori, K, Hasegawa, H, et al.. Plasma concentrations of 5-FU and creatinine clearance as predictive markers for severe toxicities of capecitabine in patients with colorectal cancer. \u2013 ASCO. J Clin Oncol 2013 31(suppl 4; abstr428). https:\/\/doi.org\/10.1200\/jco.2013.31.4-suppl.428.","DOI":"10.1200\/jco.2013.31.4_suppl.428"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_034","doi-asserted-by":"crossref","unstructured":"Meulendijks, D, Henricks, LM, Jacobs, BAW, Aliev, A, Deenen, MJ, de Vries, N, et al.. Pretreatment serum uracil concentration as a predictor of severe and fatal fluoropyrimidine-associated toxicity. Br J Cancer 2017;116:1415\u201324. https:\/\/doi.org\/10.1038\/bjc.2017.94.","DOI":"10.1038\/bjc.2017.94"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_035","doi-asserted-by":"crossref","unstructured":"van Kuilenburg, ABP, Meijer, J, Tanck, MWT, Dobritzsch, D, Zoetekouw, L, Dekkers, LL, et al.. Phenotypic and clinical implications of variants in the dihydropyrimidine dehydrogenase gene. Biochim Biophys Acta 2016;1862:754\u201362. https:\/\/doi.org\/10.1016\/j.bbadis.2016.01.009.","DOI":"10.1016\/j.bbadis.2016.01.009"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_036","doi-asserted-by":"crossref","unstructured":"Jacobs, BAW, Deenen, MJ, Pluim, D, van Hasselt, JGC, Kr\u00e4henb\u00fchl, MD, van Geel, RMJM, et al.. Pronounced between-subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers. Br J Clin Pharmacol 2016;82:706\u201316. https:\/\/doi.org\/10.1111\/bcp.13007.","DOI":"10.1111\/bcp.13007"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_037","doi-asserted-by":"crossref","unstructured":"Maillard, M, Launay, M, Royer, B, Guitton, J, Gautier-Veyret, E, Broutin, S, et al.. Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency. Br J Clin Pharmacol 2023;89:762\u201372. https:\/\/doi.org\/10.1111\/bcp.15536.","DOI":"10.1111\/bcp.15536"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_038","doi-asserted-by":"crossref","unstructured":"de With, M, Knikman, J, de Man, FM, Lunenburg, CATC, Henricks, LM, van Kuilenburg, ABP, et al.. Dihydropyrimidine dehydrogenase phenotyping using pretreatment uracil: a note of caution based on a large prospective clinical study. Clin Pharmacol Ther 2022;112:62\u20138. https:\/\/doi.org\/10.1002\/cpt.2608.","DOI":"10.1002\/cpt.2608"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_039","doi-asserted-by":"crossref","unstructured":"van Staveren, MC, van Kuilenburg, ABP, Guchelaar, HJ, Meijer, J, Punt, CJA, de Jong, RS, et al.. Evaluation of an oral uracil loading test to identify DPD-deficient patients using a limited sampling strategy. Br J Clin Pharmacol 2016;81:553\u201361. https:\/\/doi.org\/10.1111\/bcp.12821.","DOI":"10.1111\/bcp.12821"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_040","doi-asserted-by":"crossref","unstructured":"Knikman, JE, de With, M, Heersche, N, Lopez-Yurda, M, Baars, A, Creemers, GJ, et al.. Dose-individualisation of fluoropyrimidines based on pre-treatment serum uracil levels: the Alpe2U study. Eur J Cancer 2025;224:115483. https:\/\/doi.org\/10.1016\/j.ejca.2025.115483.","DOI":"10.1016\/j.ejca.2025.115483"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_041","doi-asserted-by":"crossref","unstructured":"Fiebrich-Westra, HB, Haroun, C, van der Gali\u00ebn, R, den Besten-Bertholee, D, Deenen, MJ, Moes, DJAR, et al.. Precision treatment of patients with GI cancer using pre-emptive DPYD genotyping\/phenotyping plus pharmacokinetic-guided dosing of 5-fluorouracil. JCO Precis Oncol 2025;9:e2500062. https:\/\/doi.org\/10.1200\/po-25-00062.","DOI":"10.1200\/PO-25-00062"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_042","doi-asserted-by":"crossref","unstructured":"Knikman, JE, Wilting, TA, Lopez-Yurda, M, Henricks, LM, Lunenburg, CATC, de Man, FM, et al.. Survival of patients with cancer with DPYD variant alleles and dose-individualized fluoropyrimidine therapy-a matched-pair analysis. J\u00a0Clin Oncol 2023;41:5411\u201321. https:\/\/doi.org\/10.1200\/jco.22.02780.","DOI":"10.1200\/JCO.22.02780"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_043","doi-asserted-by":"crossref","unstructured":"Glewis, S, Michael, M, Gurney, H, Olver, I, Zdenkowski, N, Ackland, S, et al.. Feasibility and population exposure of 5-fluorouracil using therapeutic drug monitoring (PREDICT-5FU): a multicentre clinical trial. Br J Clin Pharmacol 2025;91:1965\u201374. https:\/\/doi.org\/10.1002\/bcp.70006.","DOI":"10.1002\/bcp.70006"},{"key":"2025121815555029461_j_cclm-2025-0949_ref_044","doi-asserted-by":"crossref","unstructured":"Li, M, Mindt, S, L\u00fcck, A, Hutzschenreuter, U, Kollendt, M, Lathan, B, et al.. Drug monitoring detects under- and overdosing in patients receiving 5-fluorouracil-containing chemotherapy-results of a prospective, multicenter German observational study. ESMO Open 2023;8:101201. https:\/\/doi.org\/10.1016\/j.esmoop.2023.101201.","DOI":"10.1016\/j.esmoop.2023.101201"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0949\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0949\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T15:56:53Z","timestamp":1766073413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0949\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,6,23]]},"published-print":{"date-parts":[[2026,1,27]]}},"alternative-id":["10.1515\/cclm-2025-0949"],"URL":"https:\/\/doi.org\/10.1515\/cclm-2025-0949","relation":{},"ISSN":["1434-6621","1437-4331"],"issn-type":[{"value":"1434-6621","type":"print"},{"value":"1437-4331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,10]]}}}