title: Influence of vasomodulators and tumor transplantation on the disposition of 5-fluorouracil after application to the liver surface in rats.
abstract: This study investigated the effect of epinephrine (a vasoconstrictor) and hydralazine (a vasodilator) on the hepatic disposition of 5-fluorouracil (5-FU) after application to the surface of the liver in rats. Normal livers were compared with a Walker 256 carcinoma cell tumor model. A cylindrical diffusion cell was attached to the liver surface. 5-Fluorouracil was added into the diffusion cell in combination with vasomodulators or after pretreatment with epinephrine. After selected treatment times, the 5-FU concentrations were assayed at three sites in the excised livers. The 5-FU concentration in the region under the cell attachment site (site 1) was significantly higher after concomitant application of 5-FU and epinephrine, compared with 5-FU alone, and increased in an epinephrine dose-dependent manner. On the other hand, preferential distribution of 5-FU at site 1 was not seen when applied in combination with hydralazine. After 10 min of epinephrine pretreatment, the concentration of 5-FU at site 1 was approximately two times higher than that for the control. Furthermore, the 5-FU concentration at site 1 of the tumor model was greatly increased compared with the normal liver. These results suggest that application of epinephrine to the liver surface might enhance the accumulation of 5-FU at the desired target site.
authors.affiliation: Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Horishita
authors.affiliation: Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tokunaga
authors.affiliation: Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Miyamoto
authors.affiliation: Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Nakamura
authors.affiliation: Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Koyo
authors.identifier: http://orcid.org/0000-0003-4714-0978
authors.initials: K
authors.lastname: Nishida
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D002279:Carcinoma 256, Walker / Q000378:metabolism*; D045744:Cell Line, Tumor; D004837:Epinephrine / Q000494:pharmacology; D005472:Fluorouracil / Q000493:pharmacokinetics*; D006830:Hydralazine / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D006830:Hydralazine; D005472:Fluorouracil; D004837:Epinephrine
keywords: 5-fluorouracil; epinephrine; hydralazine; liver surface application; tumor surface application