• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Comprehensive analysis of influencing factor of effect/adverse effect for anti-cancer drug using virtual clinical study

Research Project

Project/Area Number 16K18972
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Toshimoto Kota  国立研究開発法人理化学研究所, イノベーション推進センター, 特別研究員 (70740504)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords薬物動態学 / モデリング&シミュレーション / 遺伝子多型 / 仮想臨床試験 / 個別医療
Outline of Final Research Achievements

Various factors such as genetic polymorphism, which leading pharmacological and toxicological effects of anti-cancer drugs, are reported among clinical studies. The aim of this research is to predict what factor is the most effective using computational virtual clinical study (VCS). Mathematical models are required to perform VCS. Because the mathematical models of anti-cancer drugs are complicated, the conventional parameter estimation method could not be applied. To overcome this problem, a new parameter optimization algorithm were newly introduced. The mathematical models which can be reproduced clinical observed plasma concentration-time profiles of drug were successfully obtained. By performing VCS, we could quantitatively predict how many times the statistical significance for each genetic polymorphism.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Evaluation of Alteration in Hepatic and Intestinal BCRP Function In Vivo from ABCG2 c.421C>A Polymorphism Based on PBPK Analysis of Rosuvastatin2018

    • Author(s)
      Futatsugi Azusa、Toshimoto Kota、Yoshikado Takashi、Sugiyama Yuichi、Kato Yukio
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 46 Issue: 5 Pages: 749-757

    • DOI

      10.1124/dmd.117.078816

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Physiologically Based Pharmacokinetic Modeling of Bosentan Identifies the Saturable Hepatic Uptake As a Major Contributor to Its Nonlinear Pharmacokinetics2018

    • Author(s)
      Sato M, Toshimoto K, Tomaru A, Yoshikado T, Tanaka Y, Hisaka A, Lee W, Sugiyama Y
    • Journal Title

      Drug Metab Dispos

      Volume: 46 Issue: 5 Pages: 740-748

    • DOI

      10.1124/dmd.117.078972

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Application of PBPK modeling and virtual clinical study approaches to predict the outcomes of CYP2D6 genotype-guided dosing of tamoxifen2018

    • Author(s)
      Nakamura T, Toshimoto K, Lee W, Imamura CK, Tanigawara Y, Sugiyma Y
    • Journal Title

      CPT Pharmacometrics Syst Pharmacol

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of the change in the blood concentration-time profile caused by complex drug-drug interactions in the liver considering the enterohepatic circulation: Examining whether the inhibition constants for uptake, metabolism and biliary excretion can be recovered by the analyses using physiologically based pharmacokinetic modeling.2017

    • Author(s)
      Toshimoto K, Tomoda Y, Chiba K, Sugiyama Y.
    • Journal Title

      J Pharm Sci

      Volume: 印刷中 Issue: 9 Pages: 2727-2738

    • DOI

      10.1016/j.xphs.2017.04.057

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Is ethnic variability in the exposure to rosuvastatin explained only by genetic polymorphisms in OATP1B1 and BCRP or should the contribution of intrinsic ethnic differences in OATP1B1 be considered?2017

    • Author(s)
      Sugiyama Y, Maeda K, Toshimoto K.
    • Journal Title

      J Pharm Sci

      Volume: 印刷中 Issue: 9 Pages: 2227-2230

    • DOI

      10.1016/j.xphs.2017.04.074

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Virtual Clinical Studies to Examine the Probability Distribution of the AUC at Target Tissues Using Physiologically-Based Pharmacokinetic Modeling: Application to Analyses of the Effect of Genetic Polymorphism of Enzymes and Transporters on Irinotecan Induced Side Effects.2017

    • Author(s)
      Toshimoto K, Tomaru A, Hosokawa M, Sugiyama Y.
    • Journal Title

      Pharm Res

      Volume: 印刷中 Issue: 8 Pages: 1584-1600

    • DOI

      10.1007/s11095-017-2153-z

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Virtual Clinical Studyを用いた効率的な医薬品開発の提案2017

    • Author(s)
      年本 広太
    • Organizer
      第24回 HAB研究機構 学術年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] PBPKモデルを用いたパラメータ最適化で得られた薬物阻害定数の妥当性検証2017

    • Author(s)
      年本 広太、友田 有加菜、千葉 康司、杉山 雄一
    • Organizer
      日本薬剤学会第32年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Application of virtual clinical studies using physiologically-based pharmacokinetic modeling to analyses of the association of side effects of CPT-11 with genetic polymorphism of enzymes and transporters.2017

    • Author(s)
      Toshimoto K, Sugiyama Y
    • Organizer
      6th FIP Pharmaceutical Sciences World Congress 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prospective prediction of the clinical efficacy of tamoxifen: application of a virtual clinical study2017

    • Author(s)
      Nakamura T, Toshimoto K, Imamura CK, Tanigawara Y, Sugiyma Y
    • Organizer
      日本薬物動態学会 第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Are inhibition constants (Ki) correctly estimated using only the blood concentration time profile of substrate drugs with and without co-administration of inhibitor drugs?2016

    • Author(s)
      Toshimoto K, Tomoda Y, Chiba K, Sugiyama Y
    • Organizer
      日本薬物動態学会 第31回年会
    • Place of Presentation
      キッセイ文化ホール(長野)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] The novel physiologically based pharmacoki- netics (PBPK) model to investigate transporter-mediated disposition and clearance of metformin in humans.2016

    • Author(s)
      Nishiyama K, Toshimoto K, Ishiguro N, Sugiyama Y
    • Organizer
      日本薬物動態学会 第31回年会
    • Place of Presentation
      キッセイ文化ホール(長野)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] Prediction of inter-individual differences in pharmacokinetics and drug interactions of pravastatin using physiologically based pharmacokinetics model with Monte Carlo simulation.2016

    • Author(s)
      Matsumoto T, Toshimoto K, Chiba K, Sugiyama Y
    • Organizer
      日本薬物動態学会 第31回年会
    • Place of Presentation
      キッセイ文化ホール(長野)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi