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5-Nitrouracil stabilizes the plasma concentration values of 5-FU in colorectal cancer patients receiving capecitabine.
- Source :
-
Scientific reports [Sci Rep] 2020 Feb 17; Vol. 10 (1), pp. 2711. Date of Electronic Publication: 2020 Feb 17. - Publication Year :
- 2020
-
Abstract
- Capecitabine is selectively converted from 5'-DFUR to 5-fluorouracil (5-FU) in tumours by thymidine phosphorylase (TP). We investigated the addition of 5-nitrouracil (5-NU), a TP inhibitor, into blood samples for precise measurements of plasma 5-FU concentrations. The plasma concentration of 5-FU was measured after capecitabine administration. Two samples were obtained at 1 or 2 h after capecitabine administration and 5-NU was added to one of each pair. Samples were stored at room temperature or 4 °C and 5-FU concentrations were measured immediately or 1.5 or 3 h later. The mean plasma 5-FU concentration was significantly higher at room temperature than at 4 °C (p < 0.001). The 5-FU concentration was significantly increased in the absence of 5-NU than in the presence of 5-NU (p < 0.001). The 5-FU change in concentration was greater in the absence of 5-NU, and reached 190% of the maximum compared with baseline. A significant interaction was found between temperature and 5-NU conditions (p < 0.001). Differences between the presence or absence of 5-NU were greater at room temperature than under refrigerated conditions. 5-FU plasma concentrations after capecitabine administration varied with time, temperature, and the presence or absence of 5-NU. This indicates that plasma concentrations of 5-FU change dependent on storage conditions after blood collection.
- Subjects :
- Adult
Antimetabolites, Antineoplastic pharmacokinetics
Antimetabolites, Antineoplastic pharmacology
Biotransformation
Capecitabine pharmacokinetics
Capecitabine pharmacology
Colorectal Neoplasms enzymology
Colorectal Neoplasms genetics
Colorectal Neoplasms pathology
Female
Humans
Liver metabolism
Male
Temperature
Thymidine Phosphorylase metabolism
Time Factors
Uracil pharmacology
Antimetabolites, Antineoplastic blood
Capecitabine blood
Colorectal Neoplasms drug therapy
Fluorouracil blood
Thymidine Phosphorylase antagonists & inhibitors
Uracil analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 32066801
- Full Text :
- https://doi.org/10.1038/s41598-020-59648-2