| Project/Area Number |
07557145
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Physical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
INUI Ken-ichi Graduate School of Medicine, Kyoto University Professor, 医学研究科, 教授 (70034030)
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| Co-Investigator(Kenkyū-buntansha) |
OKUDA Masahiro Graduate School of Medicine, Kyoto University Instructor, 医学研究科, 助手 (70252426)
YANO Ikuko Graduate School of Medicine, Kyoto University Instructor, 医学研究科, 助手 (50273446)
SAITO Hideyuki Graduate School of Medicine, Kyoto University Lecturer, 医学研究科, 講師 (40225727)
HASHIMOTO Yukiya Graduate School of Medicine, Kyoto University Associate Profesor, 医学研究科, 助教授 (90228429)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1996: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1995: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | Cultured cells / LLC-PK_1 / Caco-2 / Peptide transporter / beta-Lactam antibiotics / Transcellular transport / Renal toxicity / Kinetic analysis / LLC-PK_<1-> |
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| Research Abstract |
The characterization of absorption, distribution, metabolism, excretion of xenobiotics is a important process to evaluate the drug efficacy and safety in preclinical stages. We developed the in vitro experimental systems, the intestinal/renal membrane vesicles and the cultured epithelial cells, to save the use of experimental animals. In this study, we tried to analyze the drug transport across monolayrs of renal (LLC-PK_1, OK,MDCK) and intestinal (Caco-2) cells, and to evaluate the rate limiting step in drug absorption and excretion, as follows :
1.Experimental system using cultured cell monolayrs : The intestinal and renal epithelial cells were grown on the microporous membrane filters. We examined the apical-to-basolateral and basolateral-to apical transport of drugs in relation to the cellular accumulation. This experimental system was shown to be useful for evaluate the drug transport in intestinal/renal epithelial cells.
2.Toxicity of drugs in cultured cell : The toxicity of drug in renal cells was evaluated by measuring enzyme activities of apical membrane and lysosome. We established the optimal conditions to estimate the nephrotixicity of drugs.
3.Kinetic analysis of drug transport in cell monolayrs : We developed a simple model to estimate the clearance from apical medium to cells, cells to apical medium, cells to basolateral medium, and basolateral medium to cells. The kinetic analysis of drug transport in cell monolayrs gave the useful information about the rate limiting step of drug transport and the activity of drug transporter in intestinal and renal epithelium.
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