{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:17:48Z","timestamp":1790637468884,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,1,8]],"date-time":"2016-01-08T00:00:00Z","timestamp":1452211200000},"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":[[2016,3]]},"abstract":"<jats:sec><jats:title>AIM<\/jats:title><jats:p>Dihydropyrimidine dehydrogenase (DPD) deficiency can lead to severe toxicity following 5\u2010fluorouracil (5FU) or capecitabine (CAP) treatment. Uracil (U) can be used as a probe to determine systemic DPD activity. The present study was performed to assess the sensitivity and specificity of a U loading dose for detecting DPD deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cancer patients with Common Toxicity Score (CTC) grade III or IV toxicity after the first or second cycle of 5\u2010FU or CAP treatment were asked to participate. Based on DPD activity in PBMCs, patients were divided into two groups: DPD activity in peripheral blood mononuclear cells (PBMCs) &lt;5\u00a0nmol\u00a0mg<jats:sup>\u22121<\/jats:sup>*h<jats:sup>\u22121<\/jats:sup> (deficient group) and \u2265 5\u00a0nmol\u00a0mg<jats:sup>\u22121<\/jats:sup>*h<jats:sup>\u22121<\/jats:sup>. U 500\u00a0mg\u00a0m<jats:sup>\u20132<\/jats:sup> was administered orally and plasma concentrations of U and dihydrouracil (DHU) were determined. In the deficient group, polymerase chain reaction amplification of all 23 coding exons and flanking intronic regions of <jats:italic>DPYD<\/jats:italic> was performed. A U pharmacokinetic model was developed and used to determine the maximum enzymatic conversion capacity (V<jats:sub>max<\/jats:sub>) of the DPD enzyme for each patient. The sensitivity and specificity of V<jats:sub>max,<\/jats:sub> U concentration and the U\/DHU concentration ratio were determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 47 patients were included (19 DPD deficient, 28 DPD normal). Of the pharmacokinetic parameters investigated, a sensitivity and specificity of 80% and 98%, respectively, was obtained for the U\/DHU ratio at <jats:italic>t<\/jats:italic>\u00a0=\u00a0120\u00a0min<jats:italic>.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The high sensitivity of the U\/DHU ratio at <jats:italic>t<\/jats:italic>\u00a0=\u00a0120\u00a0min for detecting DPD deficiency, as defined by DPD activity in PBMCs, showed that the oral U loading dose can effectively identify patients with reduced DPD activity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12821","type":"journal-article","created":{"date-parts":[[2015,11,9]],"date-time":"2015-11-09T20:18:47Z","timestamp":1447100327000},"page":"553-561","source":"Crossref","is-referenced-by-count":29,"title":["Evaluation of an oral uracil loading test to identify DPD\u2010deficient patients using a limited sampling strategy"],"prefix":"10.1111","volume":"81","author":[{"given":"Maurice C.","family":"van Staveren","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy Treant Healthgroup, Scheper Hospital  Emmen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre B. 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