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Precision and accuracy of clinical repeated-dose pharmacokinetic trials applying a peak-and-trough sampling design to estimate oral clearance

Research Project

Project/Area Number 20790130
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionUniversity of Toyama

Principal Investigator

TAGUCHI Masato  University of Toyama, 大学院・医学薬学研究部(薬学), 講師 (20324056)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords臨床薬学 / 薬物動態 / 臨床試験 / 個別投与設計 / 採血デザイン / 2点採血デザイン / 経口クリアランス / 臨床薬物動態試験 / カルベジロール / 心不全 / CYP2D6
Research Abstract

The area under the concentration-time curve (AUC) and/or oral clearance (CL/F) of drugs is a key pharmacokinetic parameter to evaluate drug exposure in patients. In the present study, we performed a simulation for the clinical pharmacokinetic study, in which blood was sampled at two time points corresponding to the peak concentration (C_<peak>) and trough concentration (C_<trough>) following repetitive oral drug administration to subjects. The approximate oral clearance (CL/F_<approx>) and/or an alternative oral clearance (CL/F_<exp>) were accurate for hypothetical drugs with varied pharmacokinetic properties. We performed that the peak-and-trough sampling design is promising for the clinical repeated-dose pharmacokinetic trial for drugs.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (41 results)

All 2010 2009 2008 2007 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (23 results)

  • [Journal Article] Inhibitory and stimulative effects of amiodarone on metabolism of carvedilol in human liver microsomes2010

    • Author(s)
      Horiuchi I., Kato Y., Nakamura A., Ishida K., Taguchi M., Hashimoto Y.
    • Journal Title

      Biol. Pharm. Bull. 33

      Pages: 717-720

    • NAID

      130000248026

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of the CYP1A subfamily in stereoselective metabolism of carvedilol in β-naphthoflavone- treated Caco-2 cells.2009

    • Author(s)
      Ishida K., Taguchi M., Akao T., Hashimoto Y.
    • Journal Title

      Biol. Pharm. Bull. 32

      Pages: 513-516

    • NAID

      110007122683

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Membrane transport mechanisms of mizoribine in the rat intestine and human epithelial LS180 cells.2009

    • Author(s)
      Ishida K., Takaai M., Yotsutani A., Taguchi M., Hashimoto Y.
    • Journal Title

      Biol. Pharm. Bull. 32

      Pages: 741-745

    • NAID

      110007160665

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms responsible for the altered pharmacokinetics of Bosentan: analysis utilizing rats with bile duct ligation- induced liver dysfunction.2009

    • Author(s)
      Horiuchi I., Mori YI., Taguchi M., Ichida F., Miyawaki T., Hashimoto Y.
    • Journal Title

      Biopharm. Drug Dispos. 30

      Pages: 326-333

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A simulation study to evaluate limited sampling strategies to estimate area under the curve of drug concentration versus time following repetitive oral dosing: limited sampling model versus naive trapezoidal method.2009

    • Author(s)
      Kayano Y., Horiuchi I., Mori YI., Ishida K., Saito T., Taguchi M., Hashimoto Y.
    • Journal Title

      Biol. Pharm. Bull. 32

      Pages: 1486-1490

    • NAID

      130000117270

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Temperature-dependent specific trans- port of levofloxacin in human intestinal epithelial LS180 cells.2009

    • Author(s)
      Fukumori S., Masago M., Ishida K., Kayano Y., Taguchi M., Hashimoto Y.
    • Journal Title

      Biopharm. Drug Dispos. 30

      Pages: 448-456

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A simulation study to evaluate limited sampling strategies to estimate area under the curve of drug concentration versus time following repetitive oral dosing : limited sampling model versus naive trapezoidal method.2009

    • Author(s)
      Kayano, Yuichiro
    • Journal Title

      Biol.Pharm.Bull. 32

      Pages: 1486-1490

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms responsible for the altered pharmacokinetics of Bosentan : analysis utilizing rats with bile duct ligation-induced liver dysfunction.2009

    • Author(s)
      Horiuchi, Isao
    • Journal Title

      Biopharm.Drug Dispos. 30

      Pages: 326-333

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of the CYP1A subfamily in stereoselective metabolism of carvedilol in β-naphthoflavone-treated Caco-2 cells.2009

    • Author(s)
      Ishida, Kazuya
    • Journal Title

      Biol.Pharm.Bull. 32

      Pages: 513-516

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Additional notes on clinical repeated-dose pharmacokinetic trials applying a peak- and-trough sampling design to estimate oral clearance.2008

    • Author(s)
      Takaai M., Kayano Y., Shimizu T., Taguchi M., Hashimoto Y.
    • Journal Title

      Drug Metab. Pharmaco- kinet. 23

      Pages: 128-133

    • NAID

      10024188052

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics of R- and S-carvedilol in routinely treated Japanese patients with heart failure.2008

    • Author(s)
      Horiuchi I., Nozawa T., Fujii N., Inoue H., Honda M., Shimizu T., Taguchi M., Hashimoto Y.
    • Journal Title

      Biol. Pharm. Bull. 31

      Pages: 976-980

    • NAID

      110006663963

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Taguchi M., and Hashimoto Y.: Directional trans- cellular transport of bisoprolol in P- glycoprotein-expressed LLC-GA5-COL150 cells, but not in renal epithelial LLC-PK1 Cells.2008

    • Author(s)
      Tahara K., Kagawa Y., Takaai M., Taguchi M., Hashimoto Y.
    • Journal Title

      Drug Metab. Pharmaco- kinet. 23

      Pages: 340-346

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The apical uptake transporter of levofloxacin is distinct from the peptide transporter in human intestinal epithelial Caco-2 cells.2008

    • Author(s)
      Fukumori S., Murata T., Takaai M., Tahara K., Taguchi M., Hashimoto Y.
    • Journal Title

      Drug Metab. Pharmacokinet. 23

      Pages: 373-378

    • NAID

      10024384721

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stereoselective oxidation and glucuronidation of carvedilol in human liver and intestinal microsomes.2008

    • Author(s)
      Ishida K., Taira S., Morishita H., Kayano Y., Taguchi M., Hashimoto Y.
    • Journal Title

      Biol. Pharm. Bull. 31

      Pages: 1297-1300

    • NAID

      110006684359

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Contri- bution of Na+-independent nucleoside transport to ribavirin uptake in the rat intestine and human epithelial LS180 cells.2008

    • Author(s)
      Takaai M., Morishita H., Ishida K., Taguchi M., Hashimoto Y.
    • Journal Title

      Eur. J. Pharmacol. 601

      Pages: 61-65

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics of R-and S-carvedilol in routinely treated Japanese patients with heart failure2008

    • Author(s)
      Horiuchi, Isao
    • Journal Title

      Biol. Pharm. Bull 31

      Pages: 976-980

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Additional notes on clinical repeated-dose pharmacokinetic trials applying a peak-and-trough sampling design to estimate oral clearance2008

    • Author(s)
      Takaai, Mari
    • Journal Title

      Drug Metab. Pharmacokinet 23

      Pages: 128-133

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stereoselective oxidation and glucuronidation of carvedilol in human liver and intestinal microsomes2008

    • Author(s)
      Ishida, Kazuya
    • Journal Title

      Biol. Pharm. Bull 31

      Pages: 1297-1300

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] LS180細胞を用いたミゾリビン小腸吸収の変動機構解析.2009

    • Author(s)
      四谷綾乃, 鷹合麻里, 坂本卓也, 横田篤, 堀内威佐男, 石田和也, 田口雅登, 松倉裕喜, 橋本征也
    • Organizer
      日本薬学会北陸支部第121回例会
    • Place of Presentation
      富山
    • Year and Date
      2009-12-06
    • Related Report
      2009 Final Research Report
  • [Presentation] 小児肺高血圧患者におけるボセンタンの体内動態変動性評価.2009

    • Author(s)
      田口雅登, 加藤悠也, 堀内威佐男, 橋本征也, 廣野恵一, 伊吹圭二郎, 市田蕗子, 芳村直樹, 秋田千里, 中村常之, 中山智孝, 佐地勉
    • Organizer
      第37回北陸小児肺循環研究会
    • Place of Presentation
      金沢
    • Year and Date
      2009-09-19
    • Related Report
      2009 Final Research Report
  • [Presentation] 培養ヒト腸上皮Caco-2におけるメトトレキサートの経細胞輸送機構.2009

    • Author(s)
      鷹合麻里, 坂田淳平, 石田和也, 田口雅登, 橋本征也
    • Organizer
      日本薬学会北陸支部第120回例会
    • Place of Presentation
      金沢
    • Year and Date
      2009-07-11
    • Related Report
      2009 Final Research Report
  • [Presentation] Limited sampling modelによる薬物連投時のAUC推定に対するシミュレーション評価2009

    • Author(s)
      堀内威佐男
    • Organizer
      第26回日本TDM学会・学術大会
    • Place of Presentation
      新潟
    • Year and Date
      2009-06-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] 小児肺高血圧患者におけるボセンタンの体内動態解析.2009

    • Author(s)
      田口雅登, 森ゆんい, 堀内威佐男, 橋本征也, 廣野恵一, 上勢敬一郎, 市田蕗子, 芳村直樹, 北岡千佳, 中村常之, 高月晋一, 中山智孝, 佐地勉
    • Organizer
      第15回日本小児肺循環研究会
    • Place of Presentation
      東京
    • Year and Date
      2009-02-07
    • Related Report
      2009 Final Research Report
  • [Presentation] Caco-2細胞におけるカルベジロールの立体選択的代謝機構.2009

    • Author(s)
      石田和也, 田口雅登, 赤尾光昭, 橋本征也
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Presentation] ラット小腸および培養ヒト腸上皮LS180細胞におけるミゾリビン膜輸送の特性解析.2009

    • Author(s)
      鷹合麻里, 石田和也, 四谷綾乃, 田口雅登, 橋本征也
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Presentation] 培養ヒト腸上皮Caco-2細胞を用いたメトトレキサートの消化管吸収機構解析.2009

    • Author(s)
      鷹合麻里, 坂田淳平, 石田和也, 田口雅登, 橋本征也
    • Organizer
      日本薬剤学会第24年会
    • Place of Presentation
      静岡
    • Related Report
      2009 Final Research Report
  • [Presentation] 薬物連投時のAUC推定におけるLimited Sampling Modelの精度評価.2009

    • Author(s)
      堀内威佐男, 森ゆんい, 石田和也, 萱野勇一郎, 田口雅登, 橋本征也
    • Organizer
      日本薬剤学会第24年会
    • Place of Presentation
      静岡
    • Related Report
      2009 Final Research Report
  • [Presentation] Limited sampling modelによる薬物連投時のAUC推定に対するシミュレーション評価.2009

    • Author(s)
      堀内威佐男, 森ゆんい, 石田和也, 萱野勇一郎, 田口雅登, 橋本征也
    • Organizer
      第26回日本TDM学会・学術大会
    • Place of Presentation
      新潟
    • Related Report
      2009 Final Research Report
  • [Presentation] 連投薬物のAUC推定におけるLimited sampling modelの有用性評価.2009

    • Author(s)
      田口雅登, 堀内威佐男, 森ゆんい, 萱野勇一郎, 石田和也, 橋本征也
    • Organizer
      医療薬学フォーラム
    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Presentation] 胆管結紮誘発肝障害モデルラットを用いたボセンタンの体内動態変動機構解析.2009

    • Author(s)
      田口雅登, 堀内威佐男, 森ゆんい, 市田蕗子, 宮脇利男, 橋本征也
    • Organizer
      第19回日本医療薬学会
    • Place of Presentation
      長崎
    • Related Report
      2009 Final Research Report
  • [Presentation] Absorption mechanisms of mizoribine and ribavirin in rat intestine and human epithelial LS180 cells.2009

    • Author(s)
      Ishida K., Yotsutani A., Sakamoto T., Takaai M., Taguchi M., Hashimoto Y.
    • Organizer
      日本薬物動態学会第24回年会
    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Presentation] ミゾリビンのバイオアベイラビリティの個体間変動機構.2009

    • Author(s)
      四谷綾乃, 鷹合麻里, 坂本卓也, 横田篤, 堀内威佐男, 石田和也, 田口雅登, 橋本征也, 松倉裕喜
    • Organizer
      第30回臨床薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] カルベジロールの立体選択的代謝に及ぼすアミオダロンの影響.2009

    • Author(s)
      堀内威佐男, 加藤悠也, 中村有沙, 石田和也, 田口雅登, 橋本征也
    • Organizer
      第30回臨床薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] 胆管結紮ラットを用いたボセンタンの肝クリアランス変動機構解析.2008

    • Author(s)
      森ゆんい, 掘内威佐男, 田口雅登, 市田蕗子, 橋本征也
    • Organizer
      日本薬学会北陸支部第119回例会
    • Place of Presentation
      金沢
    • Year and Date
      2008-11-09
    • Related Report
      2009 Final Research Report
  • [Presentation] Simulation for clinical repeated-dose pharmaco- kinetic trials applying a peak-and- trough sampling design to estimate oral clearance.2008

    • Author(s)
      Kayano Y., Takaai M., Ishida K., Taguchi M., Hashimoto Y.
    • Organizer
      2008 AAPS Annual Meeting and Exposition
    • Place of Presentation
      Atlanta
    • Related Report
      2009 Final Research Report
  • [Presentation] Stereo- selective oxidation and glucuronidation of carvedilol in human liver and intestinal microsomes.2008

    • Author(s)
      Ishida K., Morishita H., Kayano Y., Taguchi M., Hashimoto Y.
    • Organizer
      2008 AAPS Annual Meeting and Exposition
    • Place of Presentation
      Atlanta
    • Related Report
      2009 Final Research Report
  • [Presentation] 胆管結紮ラットを用いたボセンタンの体内動態変動機構解析.2008

    • Author(s)
      森ゆんい, 掘内威佐男, 田口雅登, 市田蕗子, 橋本征也
    • Organizer
      第29回日本臨床薬理学会年会
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report
  • [Presentation] Simulation for clinical repeated-dose pharmacokinetic trials applying a peak-and-trough sampling design to estimate oral clearance2008

    • Author(s)
      Kayano, Yuichiro
    • Organizer
      2008 AAPS Annual Meeting and Exposition
    • Place of Presentation
      Atlanta
    • Related Report
      2008 Annual Research Report
  • [Presentation] 2点採血デザインを用いた探索的臨床薬物動態試験の有用性評価.2007

    • Author(s)
      田口雅登, 鷹合麻里, 石田和也, 萱野勇一郎, 橋本征也
    • Organizer
      医療薬学フォーラム2008第16回クリニカルファーマシーシンポジウム
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report
  • [Presentation] Characterization of levofloxacin trans- port in human intestinal LS180 cells.

    • Author(s)
      Fukumori S., Masago M., Ishida K., Kayano Y., Taguchi M., Hashimoto Y.
    • Organizer
      第23回日本薬物動態学会年会
    • Place of Presentation
      熊本
    • Related Report
      2009 Final Research Report
  • [Presentation] Pharmaco- kinetics of bosentan in rats with bile duct ligation-induced liver dysfunction.

    • Author(s)
      Horiuchi I., Mori Y., Taguchi M., Ichida F., Hashimoto Y.
    • Organizer
      第23回日本薬物動態学会年会
    • Place of Presentation
      熊本
    • Related Report
      2009 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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