首页 | 本学科首页   官方微博 | 高级检索  
     


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
Authors:Koyo?Nishida  author-information"  >  author-information__contact u-icon-before"  >  mailto:koyo-n@net.nagasaki-u.ac.jp"   title="  koyo-n@net.nagasaki-u.ac.jp"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author,Rie?Fujiwara,Yukinobu?Kodama,Shintaro?Fumoto,Takahiro?Mukai,Mikiro?Nakashima,Hitoshi?Sasaki,Junzo?Nakamura
Affiliation:(1) Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan;(2) Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Abstract:Purpose 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.Conclusion These results demonstrate the possibility of regional delivery of drugs to the liver by application to the liver surface.
Keywords:absorption  5-fluorouracil  liver surface  liver targeting  regional delivery
本文献已被 PubMed SpringerLink 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号