1989 Fiscal Year Final Research Report Summary
Establishment of a new theory for assessment of drug disposition
| Project/Area Number |
63571093
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
HASHIDA Mitsuru Kyoto University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (20135594)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAKURA Yoshinobu Kyoto University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (30171432)
YAMAMOTO Akira Kyoto University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (00166779)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Chemotherapy / Tissue Transport / Organ Perfusion Experiment / Isolated Tumor Preparation / Moment Analysis / Lipophilic Prodrug / Macromolecular Prodrug / Antibody Conjugate |
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| Research Abstract |
In chemotherapy, an efficacy of drug transport to the disease site is one of the most important factors deciding final therapeutic success. However, there is a few experimental methodologies for quantative assessment of drug disposition in the organ and we have no detailed information about drug transport under the pathological condition. In this investigation, we have tried to establish a new approach from the two directions of developments of organ perfusion technique and pharmacokinetic analysis theory. Concerning the organ perfusion technique, we have established new experimental methods for perfusion of rabbit thigh muscle with or without VX_2carcinoma and isolated tumor preparation of rat Walker256 iumor in addition to ordinary perfusion systems of the liver and kidney. On the other hand, we have derived new analytical method for local disposition of drugs based on the statistical moment analysis concept. With these methods, we have evaluated tissue transport of various targeting systems such as lipophilic and macromolecular prodrugs and elucidated the relationships between their physicochemical and biological characteristics and targeting abilities.
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