2002 Fiscal Year Final Research Report Summary
Liver-selective delivery of 5-fluorouracil utilizing the absorption on the liver surface in rats
| Project/Area Number |
13672255
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAKAMURA Junzo Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30115901)
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| Co-Investigator(Kenkyū-buntansha) |
NAKASHIMA Mikiro Nagasaki University, School of Medicine, Department of Hospital Pharmacy, Associate Professor, 医学部附属病院, 助教授 (00260737)
SAKAEDA Toshiyuki Kobe University, Department of Hospital Pharmacy, School of Medicine, Associate Professor, 医学部附属病院, 助教授 (00304098)
NISHIDA Koyo Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20237704)
MUKAI Takahiro Kyoto University Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (30284706)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Liver / Drug targeting / Liver surface application / 5-Fluorouracil / Drug delivery system / Rat / Anticancer agent / Cancer chemotherapy |
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| Research Abstract |
The liver plays an important role in maintaining homeostasis, thus many liver diseases such as hepatitis, cirrhosis and hepatoma are lethal. Although the anticancer drugs are administered orally, intravenously and intraarterially in the chemotherapy of hepatoma, the anticancer drugs are distributed to the whole body via the blood stream following the administration, leading to the inadequate liver- and lobe-selective drug delivery. The present study was undertaken to elucidate the liver- and lobe-selective delivery of 5-fluorouracil (5-FU) following the liver surface application in rats. We selected an experimental system utilizing a cylindrical diffusion cell attached to the liver surface. After liver surface application of 5-FU, 5-FU was absorbed approximately 70 % in 360 min. A semi-log plot of the remaining amount of 5-FU in the diffusion cell gave a straight line. The 5-FU concentration at lobes of the liver after intravenous administration was similar. In contrast, 5-FU was site-selectively delivered in the liver after liver surface application. From these results, we demonstrated that the absorption of 5-FU on the liver surface in rats is explained mostly by passive diffusion. Furthermore, it is elucidated the liver- and lobe-selective delivery of 5-FU following the liver surface application in rats.
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