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标题：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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作者：Yukinobu Kodama ; Shintaro Fumoto ; Junya Nishi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：5
页码：1049-1052
DOI：10.1248/bpb.31.1049
出版社：The Pharmaceutical Society of Japan
摘要：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, P _app, and the reciprocal of the square root of the molecular weight of several compounds including 5-FU. The estimated P _app 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.
关键词：chemotherapy;5-fluorouracil;liver surface;pharmacokinetics