Acyclothymidine Alleviates Intestinal Toxicity of 5'-Deoxy-5-fluorouridine without Loss of Antitumor Activity in Mice.

• HAMADA Akinobu

• FUKUSHIMA Shoji

• SANEYOSHI Mineo

• SHIMIZU Satoshi

• KAWAGUCHI Takeo

• NAKANO Masahiro

Abstract

To reduce the intestinal toxicity of orally administered 5'-deoxy-5-fluorouridine (5'-DFUR) in mice, we co-administered 5'-DFUR with acyclothymidine [AcyT, 5-methyl-(2'-hydroxyethoxymethyl) uracil], a potent inhibitor of pyrimidine nucleoside phosphorylase (PyNPase). Orally administered 5'-DFUR alone caused intestinal toxicity and severe damage to the intestinal villi, while 5'-DFUR with AcyT reduced the intestinal toxicity, and prevented damage to the intestinal villi. This toxicity arising from orally administered 5'-DFUR could not be reduced by intravenous administration of AcyT, but was alleviated by oral administration. Orally co-administered AcyT showed little effect on antitumor activity of 5'-DFUR toward subcutaneously implanted Lewis lung carcinoma, though the intestinal toxicity was reduced in the tumor-bearing mice. This finding suggests that orally co-administered AcyT may prevent the undesirable conversion of 5'-DFUR to 5-FU by PyNPase during the process of absorption in the intestinal tract.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 19 (10), 1362-1366, 1996

  The Pharmaceutical Society of Japan

Keywords

• 5'-deoxy-5-fluorouridine
• 5-fluorouracil
• pyrimidine nucleoside phosphorylase
• acyclothymidine
• intestinal toxicity

Details

• CRID: 1390001204622152832
• NII Article ID: 110003641104
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.19.1362
• ISSN: 13475215
• ISSN: 09186158
• PubMed: 8913513
• Web Site: http://www.jstage.jst.go.jp/article/bpb1993/19/10/19_10_1362/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/1997103929
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed