Influence of liver disease on phenolsulfonphthalein absorption from liver surface to examine possibility of direct liver surface application for drug targeting,
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概要
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We have examined the influence of liver disease on drug absorption from the liver surface membrane, regarded as the first barrier for drug targeting to the liver. The main purpose of this study is to examine the possibility of direct liver surface application as a drug targeting method. We employed rats intoxicated with carbon tetrachloride (CCl(4)) or D-galactosamine (GAL) as the liver disease model, and examined drug absorption characteristics after application to the liver surface, by utilizing a cylindrical diffusion cell. In the liver-intoxicated rats, about 90% of a low molecular weight drug, phenolsulfonphthalein (PSP), as a model was absorbed from the liver surface in 6 h, similar to the normal rats (no treatment). Although the absorption rate was increased in the CCl(4) group, whereas slightly retarded absorption was observed in GAL group, there should be no serious problem for the clinical use of liver surface application. The PSP absorption from the liver surface in the CCl(4) group was indicated to obey first-order kinetics by elimination profile from the diffusion cell. The first-order absorption rate constant K(a) values of PSP from the liver surface, obtained by a compartment model and elimination profile, were increased 1.3-fold in the CCl(4) group compared to the control. Moreover, we performed drug application to the liver surface in the peritoneal cavity to assume clinical use. The K(a) of PSP in the CCl(4) group was about 4-fold larger than in the normal group, implying the importance of estimating changes in peritoneal drug absorption as a result of liver disease. Consequently, it is expected that there will be no marked decline in the absorption rate from the liver surface in a liver disease state, leading us to apply this administration method for liver targeting.
- 公益社団法人日本薬学会の論文
- 2003-07-01
著者
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中島 幹夫
佐賀大学医学部附属病院 手術部
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中村 純三
Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.
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NISHIDA Koyo
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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NAKAMURA Junzo
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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NAKASHIMA Mikiro
Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry
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SASAKI Hitoshi
Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry
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Nakamura J
Faculty Of Pharmaceutical Sciences Nagasaki University
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Nakamura Junzo
長崎大学 薬
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Nakamura Junzo
School Of Pharmaceutical Sciences Nagasaki University
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Nishida K
Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.
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Nakashima M
Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.
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Nakashima Mikiro
Department Of Hospital Pharmacy Nagasaki University School Of Medicine
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Sasaki H
Dep. Of Hospital Pharmacy Nagasaki Univ. Hospital
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Nakano M
Department Of Laboratory Medicine Nagasaki University School Of Medicine
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Sasaki Hitoshi
長崎大学 医歯学部病院薬剤部
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Sasaki Hitoshi
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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HONDA Tominori
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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Honda Tominori
Department Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki University
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Nakashima Mikiro
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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