Evaluation of 5-FU plasma concentration by 13C breath test in patients treated with oral 5-FU analogs

Masaharu Higashida, Hideo Matsumoto, Hisako Kubota, Haruaki Murakami, Yukiko Kawabe, Hiroshi Nakashima, Yasuo Oka, Hideo Okumura, Masafumi Nakamura, Toshihiro Hirai

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aim: The objective of this study was to investigate the influence of digestive gastrointestinal absorption function on the pharmacokinetics of the orally-administered anticancer drug, Tegafur-gimestat-otastat potassium (TS-1), by measuring the plasma 5-fluorouracil (5-FU) concentration using stable isotope breath tests. Patients and Methods: Twenty-nine patients with progressive/recurrent digestive organ cancer were enrolled for this pharmacokinetic study, and blood samples were obtained from each patient. The area under-the-time-concentration curve between 0 and 480 min ( AUC0-480 min), time-of-drug concentration peak (Tmax), maximum drug concentration (Cmax) and the half-life period (t1/2) of 5-FU were investigated. Simultaneously, a continuous 13C-acetate breath test was performed for each patient. The parameters measured with the breath test were the area under the 13CO2 excretion rate curve between 0-4 h (AUC 0-4h), peak 13CO2 value and elimination rate constant (Kel) value. Results: The AUC0-8h and C max of 5-FU were significantly correlated with Kel (p=0.012 and p=0.024, respectively), and the 5-FU Cmax value was significantly correlated with the peak value of 13CO2 (p=0.037). Multivariate regression analysis also found the Cmax of 5-FU to be associated with Kel (p=0.0118). The Cmax and AUC0-8hof 5-FU were also significantly correlated (p<0.0001). Conclusion: The results of this study suggest that gastrointestinal absorption is closely-related to plasma 5-FU concentration after oral administration of TS-1.

Original languageEnglish
Pages (from-to)5407-5414
Number of pages8
JournalAnticancer research
Volume32
Issue number12
Publication statusPublished - Dec 1 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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