論文

査読有り
2017年3月

Accumulation of alpha-fluoro-beta-alanine and fluoro mono acetate in a patient with 5-fluorouracil-associated hyperammonemia

CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • Yoshitaka Nishikawa
  • ,
  • Taro Funakoshi
  • ,
  • Takahiro Horimatsu
  • ,
  • Shin'ichi Miyamoto
  • ,
  • Takeshi Matsubara
  • ,
  • Motoko Yanagita
  • ,
  • Shunsaku Nakagawa
  • ,
  • Atsushi Yonezawa
  • ,
  • Kazuo Matsubara
  • ,
  • Manabu Muto

79
3
開始ページ
629
終了ページ
633
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00280-017-3249-1
出版者・発行元
SPRINGER

High-dose 5-fluorouracil (5-FU) containing chemotherapy occasionally causes hyperammonemia and can be lethal. However, the mechanism of 5FU-associated hyperammonemia has not been known. The aim of this study was to reveal the pharmacokinetics of 5-FU-associated hyperammonemia in a recurrent colorectal cancer patient with end-stage renal disease (ESRD).
We experienced a case of hyperammonemia during mFOLFOX6 plus bevacizumab therapy for recurrent colorectal cancer. He was a dialyzed patient due to diabetic nephropathy and was registered to prospective blood sampling for pharmacokinetics analysis during chemotherapy. Blood concentrations of 5-FU and its catabolites were determined by inductively coupled plasma-mass spectrometry.
The patient developed hyperammonemia encephalopathy 41 h after the initiation of continuous 5-FU infusion (on the third day). Before onset of hyperammonemia encephalopathy, serum alpha-fluoro-beta-alanine (FBAL, 59.2 A mu g/ml) and fluoro mono acetate (FMA, 905.8 ng/ml) were gradually increased. After hemodialysis for hyperammonemia, FBAL and FMA were collaterally decreased and his symptom was improved. Other intermediate catabolites of 5-FU, dihydrofluorouracil, and alpha-fluoro-beta-ureidopropionic acid were not changed.
We found increases of serum FBAL and FMA under the condition of hyperammonemia in the patient with ESRD during mFOLFOX6 plus bevacizumab therapy. This research supported the hypothesis that impairment of tricarboxylic acid (TCA) cycle by FMA would cause 5-FU-associated hyperammonemia.

Web of Science ® 被引用回数 : 8

リンク情報
DOI
https://doi.org/10.1007/s00280-017-3249-1
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28204913
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000397574500020&DestApp=WOS_CPL
ID情報
  • DOI : 10.1007/s00280-017-3249-1
  • ISSN : 0344-5704
  • eISSN : 1432-0843
  • PubMed ID : 28204913
  • Web of Science ID : WOS:000397574500020

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