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Effect of metabolic inhibitors on the hepatic disposition of 5-fluorouracil after application to the rat liver surface


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Title: Effect of metabolic inhibitors on the hepatic disposition of 5-fluorouracil after application to the rat liver surface
Other Titles: 肝臓表面投与後の5-fluorouracilの肝内分布に及ぼす代謝阻害剤の影響
Authors: 下川, 研太
Authors (alternative): Shimokawa, Kenta
Issue Date: 18-Mar-2016
Publisher: 日本薬学会 / The Pharmaceutical Society of Japan
Citation: Nagasaki University (長崎大学), 博士(薬学) (2016-03-18)
Abstract: We evaluated the effects of 5-fluorouracil (5-FU) metabolic inhibitors, gimeracil or uridine, on the hepatic disposition of 5-FU after application to the liver surface in rats, aiming to enhance the availability of 5-FU in the liver. 5-FU solution with or without metabolic inhibitors was applied to the rat liver surface using a cylindrical diffusion cell. The liver, blood and the remaining solution in the diffusion cell were collected at specified times, and assayed for 5-FU content. 5-FU absorption properties were not altered by addition of gimeracil and uridine. The 5-FU concentration in the diffusion cell attachment site of the rat liver (site 1) at 0.1–0.4 M ratios of gimeracil to 5-FU was significantly higher than that of the control. On the contrary, the addition of uridine did not increase the 5-FU concentration at site 1. At a 0.1 M ratio of gimeracil to 5-FU, the maximum 5-FU plasma concentration was the lowest, and the area under the 5-FU concentration–time curve at site 1 was 3.4 times greater than that of the control. We demonstrated that applying 5-FU with gimeracil to the rat liver surface could increase the availability of 5-FU in the liver.
Description: 長崎大学学位論文 学位記番号:博(医歯薬)甲第858号 学位授与年月日:平成28年3月18日 / Author: Kenta Shimokawa, Kazumi Wakasugi, Rei Tomonaga, Ken Utsunomiya, Hirotaka Miyamoto, Shintaro Fumoto, Koyo Nishida / Citation: Biological and Pharmaceutical Bulletin, 39(3), 361-367; 2016
Keywords: liver surface / 5-fluorouracil / disposition / dihydropyrimidine dehydrogenase / gimeracil / uridine
URI: http://hdl.handle.net/10069/36262
ISSN: 09186158
DOI: 10.1248/bpb.b15-00757
Relational Links: http://hdl.handle.net/10069/36523
Rights: (C) 2016 The Pharmaceutical Society of Japan
Type: Thesis or Dissertation
Text Version: ETD
Appears in Collections:dissertation

Citable URI : http://hdl.handle.net/10069/36262

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