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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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Title: Influence of liver disease on phenolsulfonphthalein absorption from liver surface to examine possibility of direct liver surface application for drug targeting,
Authors: Nishida, Koyo / Honda, Tominori / Nakashima, Mikiro / Sasaki, Hitoshi / Sakaeda, Toshiyuki / Nakamura, Junzo
Issue Date: Jul-2003
Publisher: 日本薬学会 / The Pharmaceutical Society of Japan
Citation: Biological & Pharmaceutical Bulletin, 26 (7), p.988-993, 2003
Abstract: 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.
Keywords: drug targeting / liver disease / absorption / organ surface
URI: http://hdl.handle.net/10069/6680
ISSN: 09186158
DOI: 10.1248/bpb.26.988
PubMed ID: 12843624
Relational Links: http://dx.doi.org/10.1248/bpb.26.988
Rights: Copyright (c) 2003 The Pharmaceutical Society of Japan
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/6680

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