title: Effect of Metabolic Inhibitors on the Hepatic Disposition of 5-Fluorouracil after Application to the Rat Liver Surface.
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.
authors.affiliation: Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University.
authors.forename: Kenta
authors.initials: K
authors.lastname: Shimokawa
authors.forename: Kazumi
authors.initials: K
authors.lastname: Wakasugi
authors.forename: Rei
authors.initials: R
authors.lastname: Tomonaga
authors.forename: Ken
authors.initials: K
authors.lastname: Utsunomiya
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Miyamoto
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics*; D005472:Fluorouracil / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D017208:Rats, Wistar; D014529:Uridine / Q000494:pharmacology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D011725:Pyridines; D005472:Fluorouracil; C104201:gimeracil; D014529:Uridine