@article{oai:nagasaki-u.repo.nii.ac.jp:00019944,
 author = {Kodama, Yukinobu and Fumoto, Shintaro and Nishi, Junya and Nakashima, Mikiro and Sasaki, Hitoshi and Nakamura, Junzo and Nishida, Koyo},
 issue = {5},
 journal = {Biological & Pharmaceutical Bulletin},
 month = {May},
 note = {The present study was undertaken to elucidate the absorption and distribution characteristics of 5-fluorouracil (5-FU) after its application to the liver surface in rats to examine the possibility of reducing the systemic side effects of this agent. 5-FU was applied to the surface of the liver by employing a cylindrical diffusion cell. Approximately 69% of the dose was absorbed in 360 min. The time course of the change in the amount of 5-FU remaining in the diffusion cell obeyed first-order kinetics. Also, a linear relationship was observed between the apparent permeability coefficient, Papp, and the reciprocal of the square root of the molecular weight of several compounds including 5-FU. The estimated Papp value of 5-FU was in good agreement with the experimental value. The plasma concentration of 5-FU was low (<1.2 μg/ml) until 360 min after the application. Following i.v. administration, 5-FU was rapidly eliminated from the plasma and could not be detected at 120 min. In the analysis of tissue distribution, the liver was divided into three sites; the region under the diffusion cell attachment site (site 1), the treated lobe excluding site 1 (site 2), and untreated lobes (site 3). After being administered i.v., 5-FU mainly distributed in the kidney, and the concentration in the liver was significantly lower than that in kidney, spleen, or heart. After its application to the liver surface, however, 5-FU preferentially distributed at site 1, and was not detected at the other sites or in other tissues. Thus, these results suggested the possibility of a reduction in the systemic side effect of 5-FU on its application to the liver surface., Biological & Pharmaceutical Bulletin, 31(5), pp.1049-1052; 2008},
 pages = {1049--1052},
 title = {Absorption and Distribution Characteristics of 5-Fluorouracil (5-FU) after an Application to the Liver Surface in Rats in Order to Reduce Systemic Side Effects},
 volume = {31},
 year = {2008}
}