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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

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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.

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Abbreviations

AUC:

area under the curve

FD-4:

fluorescein isothiocyanate dextran (MW 4400)

5-FU:

5-fluorouracil

PSP:

phenolsulfonphthalein

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Acknowledgments

We wish to thank Chieko Kaneko, Masayo Shimomura, and Miyuki Horishita for their skilled technical assistance. This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, by a Grant-in-Aid from the Uehara Memorial Foundation, by a Grant-in-Aid from the Nakatomi Foundation and by a Grant-in-Aid for Scientific Research from the President of Nagasaki University.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan

    Koyo Nishida, Rie Fujiwara, Yukinobu Kodama, Shintaro Fumoto, Takahiro Mukai & Junzo Nakamura

  2. Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Mikiro Nakashima & Hitoshi Sasaki

Authors
  1. Koyo Nishida
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  2. Rie Fujiwara
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  3. Yukinobu Kodama
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  4. Shintaro Fumoto
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  5. Takahiro Mukai
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  6. Mikiro Nakashima
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  7. Hitoshi Sasaki
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  8. Junzo Nakamura
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Correspondence to Koyo Nishida.

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Nishida, K., Fujiwara, R., Kodama, Y. et al. 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. Pharm Res 22, 1331–1337 (2005). https://doi.org/10.1007/s11095-005-5273-9

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  • DOI: https://doi.org/10.1007/s11095-005-5273-9

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