5-Nitrouracil stabilizes the plasma concentration values of 5-FU in colorectal cancer patients receiving capecitabine

Sci Rep. 2020 Feb 17;10(1):2711. doi: 10.1038/s41598-020-59648-2.

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.

MeSH terms

  • Adult
  • Antimetabolites, Antineoplastic / blood*
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Antimetabolites, Antineoplastic / pharmacology
  • Biotransformation
  • Capecitabine / blood*
  • Capecitabine / pharmacokinetics
  • Capecitabine / pharmacology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Female
  • Fluorouracil / blood*
  • Humans
  • Liver / metabolism
  • Male
  • Temperature
  • Thymidine Phosphorylase / antagonists & inhibitors*
  • Thymidine Phosphorylase / metabolism
  • Time Factors
  • Uracil / analogs & derivatives*
  • Uracil / pharmacology

Substances

  • Antimetabolites, Antineoplastic
  • Uracil
  • 5-nitrouracil
  • Capecitabine
  • Thymidine Phosphorylase
  • Fluorouracil