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Establishment of a new theory for assessment of drug disposition

Research Project

Project/Area Number 63571093
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 応用薬理学・医療系薬学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

HASHIDA Mitsuru  Kyoto University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (20135594)

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)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1988: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsChemotherapy / Tissue Transport / Organ Perfusion Experiment / Isolated Tumor Preparation / Moment Analysis / Lipophilic Prodrug / Macromolecular Prodrug / Antibody Conjugate / 臓器潅流実験 / 薬物組織移行性 / モーメント解析 / 抗癌剤 / 癌病巣モデル / プロドラッグ / ドラッグデリバリーシステム
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.

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Toshiyuki Kakutani: "Effect of plasma protein binding on drug disposition in musle tissue:Application of statisical moment analysis and net work theory to in situ local single-pass perfusion system" Journal of Pharmacokinetics and Biopharmaceutics. 16. 129-149 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hitoshi Sezaki: "Control of pharmaceutical propertieal by dextran conjugates" Journal of Bioactive and Compatible Polymers. 3. 81-85 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsuru Hashida: "Characterization of lipophilic prodrug of 5-fluorouracil with a cholesterol promoiety and its application to liposomes" Chemical and Pharmaceutical Bulletin. 36. 3186-3189 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kimihiko Sato: "Disposition of a polymeric prodrug of mitomycin C,mitomycin C-dextran conjugate,in the perfused rat liver" Journal of Pharmaceutical Sciences. 78. 11-16 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Koyo Nishida: "Statistical moment analysis of hepatobiliary transport of phenol red in the perfused rat liver" Pharmaceutical Research. 6. 140-146 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hitoshi Sezaki: "Soluble macromolecular carriers for the delivery of antitumor drugs" Advanced drug Delivery Reviews. 3. 247-266 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 橋田充: "高分子修飾マイトマイシンCの合成と薬効" 有機合成化学. 46. 776-788 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 橋田充: "薬物タ-ゲティング方式の分類とその理論" 日本臨床. 47. 1240-1248 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsuru Hashida: "Control of pharmacokinetic profiles of mitomycin C by dextran conjugation.In“Xenobiotic Metabolism and Disposition".Eds.by R.Kato,R.W.Estabrook,and M.N.Cayen" Taylor and Francis, 6 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Toshiyuki Kakutani: "Effect of plasma protein binding on drug disposition in muscle tissue: Application of statistical moment analysis and net work theory to in situ local single-pass perfusion system." Journal of Pharmacokinetics and Biopharmaceutics 16, 129-149 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hitoshi Sezaki: "Control of pharmaceutical properties by dextran conjugates." Journal of Bioactive and Compatible Polymers 3, 81-85 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsuru Hashida: "Characterization of lipophilic prodrug of 5-fluorouracil with a cholesterol promoiety and its application to liposomes." Chemical and Pharmaceutical Bulletin 36, 3186-3189 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kimihiko Sato: "Disposition of a polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate, in the perfused rat liver." Journal of Pharmaceutical Sciences 78, 11-16 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Koyo Nishida: "Statistical moment analysis of hepatobiliary transport of phenol red in the perfused rat liver." Pharmaceutical Research 6, 140-146 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hitoshi Sezaki: "Soluble macromolecular carriers for the delivery of antitumor drugs." Advanced Drug Delivery Reviews 3, 247-266 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsuru Hashida: "Synthesis and antitumor activity of macromolecular derivatives of mitomycin C. (Japanese)" Yukigosei Kagaku 46, 776-788 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsuru Hashida: "Theory and methods of drug targeting. (Japanese)" Nippon Rinsho 47, 1240-1248 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mitsuru Hashida: "Control of pharmacokinetic profile of mitomycin C by dextran conjugation." Xenobiotic Metabolism and Disposition Taylor and Francis, (1989) pp.531-538.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kimihiko Sato: "Disposition of a polymeric prodrug of mitomycin C,mitomycin C-dextran conjugate,in the perfused rat liver" Journal of Pharmaceutical Sciences. 78. 11-16 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Koyo Nishida: "Statistical moment analysis of hepatobiliary transport of phenol red in the perfused rat liver" Pharmaceutical Research. 6. 140-146 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Hitoshi Sezaki: "Soluble macromolecular carriers for the delivery of antitumor drugs" Advanced Drug Delivery Reviews. 3. 247-266 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 橋田充: "薬物タ-ゲティング方式の分類とその理論" 日本臨床. 47. 1240-1248 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Toshiyuki Kakutani: Journal of Pharmacokinetics and Biopharmaceutics. 16. 129-149 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Hitoshi Sezaki: Journal of Bioactive and Compatible Polymers. 3. 81-85 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Mitsuru Hashida: Chemical and Pharmaceutical Bulletin. 36. 3186-3189 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kimihiko Sato: Journal of Pharmaceutical Sciences. 78. 11-16 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Koyo Nishida: Pharmaceutical Research. 6. 140-146 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 橋田充: 有機合成化学. 46. 776-788 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Hashida,Mitsuru: "Control of pharmacokinetic profiles of mitomycin C by dextran conjugation.In"Xenobiotic Metabolism and Disposition"." Taylor and Francis, 531-538 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 橋田充: "「ドラックデリバリーシステム」(続タンパク質ハイブリッド:これからの化学修飾第6章)" 共立出版, 132-166 (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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