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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


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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
Authors: Kodama, Yukinobu / Fumoto, Shintaro / Nishi, Junya / Nakashima, Mikiro / Sasaki, Hitoshi / Nakamura, Junzo / Nishida, Koyo
Issue Date: 1-May-2008
Publisher: The Pharmaceutical Society of Japan
Citation: Biological & Pharmaceutical Bulletin, 31(5), pp.1049-1052; 2008
Abstract: 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.
Keywords: chemotherapy / 5-fluorouracil / liver surface / pharmacokinetics
URI: http://hdl.handle.net/10069/17918
ISSN: 09186158
DOI: 10.1248/bpb.31.1049
Rights: (c) 2008 The Pharmaceutical Society of Japan
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/17918

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