{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:06:08Z","timestamp":1779894368068,"version":"3.53.1"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,7,26]],"date-time":"2020-07-26T00:00:00Z","timestamp":1595721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>5\u2010Fluorouracil (5\u2010FU) is widely used in combination chemotherapy, and literature suggests pharmacokinetic\u2010guided dosing to improve clinical efficacy and reduce toxicity. This study aimed to determine the pharmacokinetic exposure of both 5\u2010FU and its metabolite, 5,6\u2010dihydrofluorouracil (DHFU), in patients with gastrointestinal malignancy and to establish a simplified strategy to assist in therapeutic drug management for dose optimization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a prospective, observational study, performed in 27 patients diagnosed with gastrointestinal malignancy who were prescribed 5\u2010FU. Multiple samples were collected per patient over the slow bolus (15\u201320 min) and continuous infusion period (over 44 h) in doses 1 and 3, and the concentrations of 5\u2010FU and DHFU were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A higher proportion of patients had exposures within the therapeutic range in dose 3 (50%) as compared to dose 1 (37.5%) with 5\u2010FU. There was an association between delayed time to maximum concentration of DHFU and a high maximum concentration of 5\u2010FU. A limited sampling strategy was developed with 4 samples, 2 during the bolus period and 2 during the continuous period (at 18 h and the end of infusion), which accurately predicted the total area under the curve of 5\u2010FU.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Using body surface area\u2010based dosing with 5\u2010FU, 50\u201360% of patients were outside of the therapeutic range. In the absence of genotype testing, measurement of the metabolite DHFU could be a phenotypical measure of dihydropyrimidine dehydrogenase enzyme activity. A limited sampling strategy was developed in patients who were prescribed a combination regimen of slow bolus, followed by a 44\u2010hour continuous infusion of 5\u2010FU to assist in the therapeutic drug management of patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14444","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T17:23:25Z","timestamp":1593278605000},"page":"937-945","source":"Crossref","is-referenced-by-count":7,"title":["Systemic exposure to 5\u2010fluorouracil and its metabolite, 5,6\u2010dihydrofluorouracil, and development of a limited sampling strategy for therapeutic drug management of 5\u2010fluorouracil in patients with gastrointestinal malignancy"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-9750","authenticated-orcid":false,"given":"Jeana","family":"Jacob","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology Christian Medical College and Hospital  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-2392","authenticated-orcid":false,"given":"Sumith K.","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology Christian Medical College and Hospital  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju Titus","family":"Chacko","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Christian Medical College and Hospital  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blessed Winston","family":"Aruldhas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology Christian Medical College and Hospital  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Christian Medical College and Hospital  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratna","family":"Prabha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology Christian Medical College and Hospital  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binu Susan","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology Christian Medical College and Hospital  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2004.01.006"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012294617392"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200210000-00002"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.3934"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.4.1470"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19960201)77:3<441::AID-CNCR4>3.0.CO;2-N"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clcc.2012.05.004"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2014-0132"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clcc.2016.04.001"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1124"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000238"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1989.59"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clcc.2013.11.001"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1529"},{"key":"e_1_2_11_16_1","unstructured":"Common Terminology Criteria for Adverse Events (CTCAE).Published online2017:147."},{"key":"e_1_2_11_17_1","unstructured":"R: The R Project for Statistical Computing. 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