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

下川, 研太

39 ( 3 )  , pp.361 - 367 , 2016-03-18 , 日本薬学会 / The Pharmaceutical Society of Japan
ISSN:09186158
Description
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.
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http://naosite.lb.nagasaki-u.ac.jp/dspace/bitstream/10069/36262/1/ISYK858_Shimokawa.pdf

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