Rie Fujiwara

Nagasaki University, Nagasaki, Nagasaki, Japan

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Publications (2)3.42 Total impact

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    ABSTRACT: The purpose of this study was to examine drug distribution in the liver after drug application to the rat liver surface. 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). 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. These results demonstrate the possibility of regional delivery of drugs to the liver by application to the liver surface.
    Pharmaceutical Research 09/2005; 22(8):1331-7. DOI:10.1007/s11095-005-5273-9 · 3.42 Impact Factor
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    ABSTRACT: We have proposed the organ surface as a novel application site of drugs, and elucidated the absorption mechanism from the organ surface. In the present study, we examined the drug distribution after application to the rat liver and kidney surface and evaluated possibility of site-selective drug targeting to the organ. We selected phenol red (PR), FITC-dextran (FD-4, Mw 4, 400), and 5-FU as model drugs. The concentration of the model drugs at the administered site after application to the rat liver surface was significantly higher than those in the other two sites. In addition, the concentration of PR and 5-FU in the right kidney after application to the rat right kidney surface was high compared with that in the left kidney, although no significant difference was observed in FD-4. A similar tendency was observed in the urinary excretion rate. Moreover, selectivity advantage of the organ surface application was proven kinetically based on the physiological model. Consequently, drug application to the organ surface could improve availability in the desired site of a new drug such as genome medicine.
    01/2001; 16(supplement):116-117. DOI:10.2133/dmpk.16.supplement_116