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Analysis of dissolution kinetics and first-pass elimination of orally administered drugs and its application to prediction of absorption behavior after oral administration

Research Project

Project/Area Number 21590158
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionOkayama University

Principal Investigator

KIMURA Toshikiro  岡山大学, 大学院・医歯薬学総合研究科, 特命教授 (10025710)

Co-Investigator(Kenkyū-buntansha) HIGAKI Kazutaka  岡山大学, 大学院・医歯薬学総合研究科, 教授 (60284080)
OGAWARA Kenichi  岡山大学, 大学院・医歯薬学総合研究科, 准教授 (30291470)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords消化管吸収 / 初回通過効果 / 難溶解性薬物 / P-glycoprotein / Cytochrome P450 3A / 自己乳化型マイクロエマルション製剤(SMEDDS) / 経口吸収 / 自己乳化型マイクロエマルション製剤 / 胆汁 / 膵リパーゼ / 放出 / グリセオフルビン / ムチン層 / griseofulvin / 自己乳化型マイクロエマルション / 油脂成分 / 界面活性剤 / 補助界面活性剤 / SMEDDS製剤 / 経口投与 / 経口窒収 / quinidine / 発現タンパク量 / 吸収クリアランス / 小腸抽出率
Research Abstract

The large variability in absorption behavior of griseofulvin would be attributed to the large variability in in vivo dissolution behavior after oral administration. We successfully described the individual absorption behavior of griseofulvin based on the data of gastrointestinal transit and the estimated in vivo dissolution behavior. SMEDDS significantly increased the bioavailability and reduced the interindividual difference in absorption behavior of griseofulvin. Both CYP3A and P-gp significantly contributed to the intestinal extraction of digoxin, but neither would affect the absorption clearance.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (36 results)

All 2011 2010 2009

All Journal Article (9 results) (of which Peer Reviewed: 2 results) Presentation (26 results) Book (1 results)

  • [Journal Article] Sex differences in pharmacokinetics of cilostazol in rats2011

    • Author(s)
      N. Kamada, K. Yamada, M. Odomi, T. Mukai, T. Nishibayashi, K. Ogawara, T. Kimura and K. Higaki
    • Journal Title

      Xenobiotica

      Volume: 41(10) Pages: 903-913

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sex differences in pharmacokinetics of cilostazol in rats2011

    • Author(s)
      Naoki Kamada
    • Journal Title

      Xenobiotica

      Volume: 41 Issue: 10 Pages: 903-913

    • DOI

      10.3109/00498254.2011.590242

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 自己乳化型マイクロエマルション製剤2010

    • Author(s)
      檜垣和孝、木村聰城郎
    • Journal Title

      J. Pharm. Sci. Technol.

      Volume: 70(1) Pages: 32-38

    • NAID

      10029100674

    • Related Report
      2011 Final Research Report
  • [Journal Article] 自己乳化型マイクロエマルション製剤2010

    • Author(s)
      檜垣和孝、木村聰城郎
    • Journal Title

      薬剤学 70

      Pages: 32-38

    • NAID

      10029100674

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2010

    • Author(s)
      檜垣和孝
    • Journal Title

      難水溶性薬物の物性評価と製剤設計の新展開(シーエムシー出版)

      Pages: 151-160

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 自己乳化型マイクロエマルション製剤による吸収改善2009

    • Author(s)
      檜垣和孝
    • Journal Title

      Farumashia

      Volume: 45(12) Pages: 1213-1216

    • Related Report
      2011 Final Research Report
  • [Journal Article] オーラルメディケーションにおける胃排出の重要性2009

    • Author(s)
      檜垣和孝
    • Journal Title

      Pharm Tech Japan

      Volume: 25(13) Pages: 48-52

    • Related Report
      2011 Final Research Report
  • [Journal Article] オーラルメディケーションにおける胃排出の重要性2009

    • Author(s)
      檜垣和孝
    • Journal Title

      ファームテクジャパン 25

      Pages: 2636-2640

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 自己乳化型マイクロエマルション製剤による吸収改善2009

    • Author(s)
      檜垣和孝
    • Journal Title

      ファルマシア 45

      Pages: 1213-1216

    • Related Report
      2009 Annual Research Report
  • [Presentation] Contribution of P-glycoprotein and Cytochrome P450 3A to intestinal first-pass disposition of loperamide in rats2011

    • Author(s)
      Arata Kuroshima
    • Organizer
      第5回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      名古屋大学医学部付属病院
    • Related Report
      2011 Final Research Report
  • [Presentation] Development of simple system for predicting oral absorption of drugs based on Gastrointestinal-Transit-Absorption(GITA) model2011

    • Author(s)
      Masato Gomi
    • Organizer
      第26回薬物動態学会年会
    • Place of Presentation
      広島国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] Contribution of P-glycoprotein and Cytochrome P450 3A to intestinal first-pass disposition of loperamide in rats2011

    • Author(s)
      Arata Kuroshima
    • Organizer
      第26回薬物動態学会年会
    • Place of Presentation
      広島国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] Prediction of oral bio-availability of drugs based on gastro-intestinal-transit absorption(GITA) model2011

    • Author(s)
      Masato Gomi
    • Organizer
      International Symposium on BA/BE of Oral Drug Products
    • Place of Presentation
      Kobe International Conference Center
    • Related Report
      2011 Final Research Report
  • [Presentation] Prediction of oral bioavailability of diugs based on gastrointestinal-transit absorption (GITA) model2011

    • Author(s)
      Masato Gomi
    • Organizer
      International symposium on BA/BE of oral drug products
    • Place of Presentation
      Kobe International Conference Center, Kobe, Japan
    • Related Report
      2011 Annual Research Report
  • [Presentation] Contribution of P-glycoprotein and Cytochrome P450 3A to intestinal first-pass disposition of loperamide in rats2011

    • Author(s)
      Arata Kuroshima
    • Organizer
      第26回薬物動態学会年会
    • Place of Presentation
      広島国際会議場,広島
    • Related Report
      2011 Annual Research Report
  • [Presentation] Development of simple system for predicting oral absorption of drugs based on gastrointestinal-transit absorption (GITA) model2011

    • Author(s)
      Masato Gomi
    • Organizer
      第26回薬物動態学会年会
    • Place of Presentation
      広島国際会議場,広島
    • Related Report
      2011 Annual Research Report
  • [Presentation] Contribution of P-glycoprotein and Cytochrome P450 3A to intestinal first-pass disposition of loperamide in rats2011

    • Author(s)
      Arata Kuroshima
    • Organizer
      第5回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      名古屋大学医学部付属病院,名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] IVIVC for oral absorp-tion of cilostazol, a BCS class II drug, based on GITA(GI-transit-absorption) model2010

    • Author(s)
      Naoki Kamada
    • Organizer
      FIP Pharmaceutical Sciences 2010 World Congress(4th PSWC)
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Prediction of oral bioavailability of drugs based on Gastro-intestinal-transit absorption(GITA) model2010

    • Author(s)
      Kazutaka Higaki
    • Organizer
      FIP Pharmaceutical Sciences 2010 World Congress(4th PSWC)
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Improvement of oral absorption behavior of digoxin by self-microemulsifying drug delivery system(SMEDDS) formulation2010

    • Author(s)
      Kensuke Horiuchi
    • Organizer
      第25回日本薬物動態学会年会
    • Place of Presentation
      大宮ソニックシティ,埼玉
    • Related Report
      2011 Final Research Report
  • [Presentation] 薬物の消化管内移行性に基づいた経口吸収予測システムの構築2010

    • Author(s)
      五味真人
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      あわぎんホール,徳島
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] ラットでのシロスタゾールの体内動態及び代謝における性差の解析2010

    • Author(s)
      鎌田直興
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      あわぎんホール,徳島
    • Related Report
      2011 Final Research Report
  • [Presentation] GI-Transit-Absorption Model(GITA Model)に基づく経口吸収動態の予測と解析2010

    • Author(s)
      堀内健佑
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      あわぎんホール,徳島
    • Related Report
      2011 Final Research Report
  • [Presentation] SMEDDSによるグリセオフルビンの吸収挙動の改善と機構解析2010

    • Author(s)
      春藤亜衣子
    • Organizer
      第130回日本薬学会
    • Place of Presentation
      岡山コンベンションセンター
    • Related Report
      2011 Final Research Report
  • [Presentation] GI-Transit-Absorption Model (GITA Mudel)に基づく経口吸収動態の予測と解析2010

    • Author(s)
      堀内健佑
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      あわぎんホール,徳島
    • Related Report
      2010 Annual Research Report
  • [Presentation] IMPROVEMENT OF ORAL ABSORPTION BEHAVIOR OF DIGOXIN BY SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM (SMEDDS) FORMULATION2010

    • Author(s)
      Kensuke Horiuchi
    • Organizer
      第25回日本薬物動態学会年会
    • Place of Presentation
      大宮ソニックシティ,埼玉
    • Related Report
      2010 Annual Research Report
  • [Presentation] SMEDDSによるグリセオフルビンの吸収挙動の改善と機構解析2010

    • Author(s)
      春藤亜衣子
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山コンベンションセンター
    • Related Report
      2009 Annual Research Report
  • [Presentation] Prediction of oral bioavailability of drugs based on Gastro-intestinal-Transit Absorption(GITA) model2009

    • Author(s)
      Shota Itokawa
    • Organizer
      第24回日本薬物動態学会年会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] Pharmacokinetic evaluation of absorption behavior of P-glycoprotein substrates based on GI-transit absorption(GITA) model2009

    • Author(s)
      Kensuke Horiuchi
    • Organizer
      第24回日本薬物動態学会年会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] IVIVC for oral absorp-tion of cilostazol, a BCS class II drug, based on GITA(GI-transit absorption) model2009

    • Author(s)
      Naoki Kamada
    • Organizer
      第24回日本薬物動態学会年会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] Contribution of P-glyco-protein and cytochrome P450 3A to intestinal first-pass disposition in rats2009

    • Author(s)
      Hitomi Koide
    • Organizer
      第24回日本薬物動態学会年会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] Importance of gastro-intestinal transit for oral medication2009

    • Author(s)
      Kazutaka Higaki
    • Organizer
      Annual conference of the German Pharmaceutical Society 2009
    • Place of Presentation
      Germany
    • Related Report
      2011 Final Research Report
  • [Presentation] 雌性ラットにおけるシロスタゾールの吸収動態の解析2009

    • Author(s)
      鎌田直興
    • Organizer
      日本薬剤学会第24年会
    • Place of Presentation
      静岡県コンベンションセンター
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Importance of gastro-intestinal transit for oral medication2009

    • Author(s)
      K.Higaki
    • Organizer
      ドイツ薬学会 2009年会(Jahrestagung der DphG 2009)
    • Place of Presentation
      Friedrich-Schiller-Universitata Jena, Deutshland
    • Related Report
      2009 Annual Research Report
  • [Presentation] PHARMACOKINETIC EVALUATION OF ABSORPTION BEHAVIOR OF P-GLYCOPROTEIN SUBSTRATES BASED ON GI-TRANSIT ABSORPTION(GITA)MODEL2009

    • Author(s)
      K.Horiuchi
    • Organizer
      第24回日本薬物動態学会年会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2009 Annual Research Report
  • [Book] 難水溶性薬物の物性評価と製剤設計の新展開第4章担体を利用した難水溶性薬物の製剤化1.自己乳化型製剤2010

    • Author(s)
      檜垣和孝, 他
    • Publisher
      シーエムシー
    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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