title: Effect of viscous additives on the absorption and hepatic disposition of 5-fluorouracil (5-FU) after application to liver surface in rats.
abstract: Objectives  The aim was to study the effect of viscous additives on the absorption and hepatic disposition of 5-fluorouracil (5-FU) after application to the liver surface in rats. Methods  5-FU solution with or without viscous additives was applied to the rat liver surface with a cylindrical diffusion cell. Then, blood and the remaining solution in the diffusion cell were collected at selected times, followed by excision of the liver. The excised liver was divided into three sites and assayed for 5-FU content. Key findings  The absorption rate of 5-FU from the liver surface was decreased in the presence of carboxymethylcellulose sodium (CMC-Na) and polyvinyl alcohol (PVA) as compared with the control. The k(a)  values of PVA 15% and CMC-Na 1% were reduced to about 80 and 67% of the control. The maximum plasma concentration of 5-FU was decreased by incorporation of viscous additives. The 5-FU concentration at the diffusion cell attachment site of the liver (site 1) plateaued at 180 min in the absence of viscous additives. On the other hand, the concentration of 5-FU at site 1 increased in a time-dependent manner until 360 min in the presence of viscous additives. Conclusion  Viscous additives might be useful for retaining drugs at their application site and controlling the rate of absorption from the liver surface.
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University Department of Hospital Pharmacy, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.forename: Miyuki
authors.initials: M
authors.lastname: Horishita
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.forename: Toyoharu
authors.initials: T
authors.lastname: Mine
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Miyamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Haruna
authors.initials: H
authors.lastname: Hirata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Junzo
authors.initials: J
authors.lastname: Nakamura
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry*; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D011142:Polyvinyl Alcohol / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014783:Viscosity
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D005079:Excipients; D011142:Polyvinyl Alcohol; D002266:Carboxymethylcellulose Sodium; D005472:Fluorouracil