title: Regional delivery of model compounds and 5-Fluorouracil to the liver by their application to the liver surface in rats: its implication for clinical use.
abstract: OBJECTIVE
  The purpose of this study was to examine drug distribution in the liver after drug application to the rat liver surface.
  
  
  METHODS
  Phenolsulfonphthalein (PSP) and fluorescein isothiocyanate dextran (MW 4400, FD-4) as model compounds or 5-fluorouracil (5-FU) was applied to the rat liver surface by employing a cylindrical diffusion cell (i.d. 9 mm, 0.64 cm2). 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: the region under the diffusion cell attachment site (site 1), the applied lobe except for site 1 (site 2), and non-applied lobes (site 3).
  
  
  RESULTS
  In the case of i.v. administration, there were no differences in PSP concentrations among the three sites of the rat liver, and the concentrations rapidly decreased. On the other hand, the PSP concentration in site 1 after application to the rat liver surface was considerably higher than in site 2 and site 3. In addition, the area under the curve (AUC) value (AUCsite1), calculated from the PSP concentration profile in site 1, was about 10 times larger than that in site 3. A similar trend of regional delivery advantage by liver surface application was observed in the case of the macromolecule model FD-4, with a marked AUCsite1 of about 5 times larger than the other two sites. Moreover, we clarified that the anticancer drug 5-FU preferentially distributed in site 1 after application to the rat liver surface.
  
  
  CONCLUSIONS
  These results demonstrate the possibility of regional delivery of drugs to the liver by application to the liver surface.
authors.affiliation: Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan. koyo-n@net.nagasaki-u.ac.jp
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
authors.forename: Rie
authors.initials: R
authors.lastname: Fujiwara
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
authors.forename: Mikiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Junzo
authors.initials: J
authors.lastname: Nakamura
mesh_terms: D000042:Absorption; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D009928:Organ Specificity; D010534:Peritoneal Neoplasms / Q000188:drug therapy; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D016650:Fluorescein-5-isothiocyanate; D010637:Phenolsulfonphthalein; D005472:Fluorouracil