dc.contributor.author |
Helsby, Nuala A |
|
dc.contributor.author |
Duley, John |
|
dc.contributor.author |
Burns, Kathryn E |
|
dc.contributor.author |
Bonnet, Claire |
|
dc.contributor.author |
Jeong, Soo Hee |
|
dc.contributor.author |
Brenman, Elliott |
|
dc.contributor.author |
Barlow, Paula |
|
dc.contributor.author |
Sharples, Katrina |
|
dc.contributor.author |
Porter, David |
|
dc.contributor.author |
Findlay, Michael |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2023-01-11T01:16:06Z |
|
dc.date.available |
2023-01-11T01:16:06Z |
|
dc.date.issued |
2020-01 |
|
dc.identifier.citation |
(2020). British Journal of Clinical Pharmacology, 86(1), 155-164. |
|
dc.identifier.issn |
0306-5251 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/62379 |
|
dc.description.abstract |
<h4>Aims</h4>A previous study suggested that a thymine (THY) challenge dose could detect aberrant pharmacokinetics in known cases of fluoropyrimidine toxicity compared with healthy volunteers. The preliminary data suggested that urine sampling also could detect this aberrant disposition. The aim of this case-control study was to assess the ability of the urinary THY challenge test to discriminate cases of severe gastrointestinal toxicity in a cohort of patients treated with 5-fluorouracil or capecitabine.<h4>Methods</h4>Patients (n = 37) received a 250 mg (per os) dose of THY and a cumulative urine sample was collected for 0-4 h. The urinary amounts of THY and metabolite dihydrothymine (DHT) were determined by liquid chromatography/mass spectrometry. Genomic DNA was analysed for DPYD gene variants. Renal function was estimated from blood creatinine levels. Cases (n = 9) and noncases (n = 23) of severe (grade ≥ 3) gastrointestinal toxicity were defined based on Common Terminology Criteria for Adverse Events.<h4>Results</h4>The median THY/DHT ratios were 6.2 (interquartile range 2.9-6.4) in cases, including the 2 patients who were DPYD heterozygous carriers. However, this was not significantly different (P = .07) from the THY/DHT in noncases (median 2.6, interquartile range 2.8-4.2). Although creatinine clearance was lower (P = .001) in cases, renal function could not discriminate cases from noncases. However, logistic regression analysis using both of these explanatory variables could discriminate most cases (receiver operating characteristic area 0.8792, 95% confidence interval 0.72-1.00).<h4>Conclusions</h4>The THY challenge test combined with a patient's renal function may be useful as a phenotypic diagnostic test to detect risk of life-threatening fluoropyrimidine gastrointestinal toxicity. |
|
dc.format.medium |
Print-Electronic |
|
dc.language |
eng |
|
dc.publisher |
Wiley |
|
dc.relation.ispartofseries |
British journal of clinical pharmacology |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.subject |
Humans |
|
dc.subject |
Fluorouracil |
|
dc.subject |
Thymine |
|
dc.subject |
Dihydrouracil Dehydrogenase (NADP) |
|
dc.subject |
Diagnostic Tests, Routine |
|
dc.subject |
Case-Control Studies |
|
dc.subject |
Capecitabine |
|
dc.subject |
anticancer drugs |
|
dc.subject |
biomarkers |
|
dc.subject |
clinical pharmacology |
|
dc.subject |
genetics and pharmacogenetics |
|
dc.subject |
medication safety |
|
dc.subject |
oncology |
|
dc.subject |
Clinical Research |
|
dc.subject |
Kidney Disease |
|
dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Pharmacology & Pharmacy |
|
dc.subject |
5-FLUOROURACIL TOXICITY |
|
dc.subject |
CLINICAL-RELEVANCE |
|
dc.subject |
DPYD VARIANTS |
|
dc.subject |
DPD ACTIVITY |
|
dc.subject |
PHARMACOKINETICS |
|
dc.subject |
METABOLITES |
|
dc.subject |
CLEARANCE |
|
dc.subject |
REGIMENS |
|
dc.subject |
EFFICACY |
|
dc.subject |
1103 Clinical Sciences |
|
dc.subject |
Clinical |
|
dc.subject |
Clinical Medicine and Science |
|
dc.subject |
1115 Pharmacology and Pharmaceutical Sciences |
|
dc.title |
A case-control study to assess the ability of the thymine challenge test to predict patients with severe to life threatening fluoropyrimidine-induced gastrointestinal toxicity. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1111/bcp.14153 |
|
pubs.issue |
1 |
|
pubs.begin-page |
155 |
|
pubs.volume |
86 |
|
dc.date.updated |
2022-12-19T21:23:01Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
31658382 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/31658382 |
|
pubs.end-page |
164 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
|
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
784809 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Science |
|
pubs.org-id |
Science Research |
|
pubs.org-id |
Medical Sciences |
|
pubs.org-id |
Molecular Medicine |
|
pubs.org-id |
Oncology |
|
pubs.org-id |
Pharmacology |
|
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
|
dc.identifier.eissn |
1365-2125 |
|
pubs.record-created-at-source-date |
2022-12-20 |
|
pubs.online-publication-date |
2019-12-12 |
|