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Novel systmen for predicting adverse effect of neuropathy in oxaliplatin based chemotherapy

Research Project

Project/Area Number 15K08085
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

Ito Yukako  京都薬科大学, 薬学部, 講師 (30278444)

Co-Investigator(Renkei-kenkyūsha) Sakaeda Toshiyuki  京都薬科大学, 薬物動態学分野, 教授 (00304098)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsPK/PD解析 / 抗がん剤 / オキサリプラチン / 末梢神経障害 / がん化学療法 / PK/PD / 個別化医療 / 大腸がん / 末しょう神経障害 / PK/PD解析
Outline of Final Research Achievements

Oxaliplatin (L-OHP) has been developed as a third-generation platinum compound for the treatment of gastroenterological cancer in chemotherapy, including FOLFOX, CapOX, SOX, and FOLFIRINOX. Undesirable side effects, such as emesis, diarrhea, nausea, vomiting, muscle pain, joint pain, and peripheral neuropathy, cause discontinuation of therapy, indicating inadequate treatment. L-OHP-induced neuropathy is predominant reason for extension of the withdrawal period, and termination of therapy. Two different strategies have been advocated to prevent L-OHP-induced neuropathy: a Stop-and -Go approach and the concurrent use of neuromodulatory agents, including antidepressants, antiepileptics, or calcium and magnesium infusions. However, neither strategy is sufficiently effective. In order to prevent serious side effects and safely complete the chemotherapy regimen, this study investigated the pharmacokinetic and toxicodynamic properties of L-OHP in colorectal cancer model rats.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (39 results)

All 2018 2017 2016 2015

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 5 results) Presentation (30 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Pharmacokinetic and toxicodynamic evaluation of oxaliplatin-induced neuropathy and hematological toxicity in rats.2018

    • Author(s)
      Yukako Ito, Shinji Kobuchi, Risa Shimizu, Yosuke Katsuyama:
    • Journal Title

      Cancer Chemother. Pharmacol.,

      Volume: 81(1): Issue: 1 Pages: 155-161

    • DOI

      10.1007/s00280-017-3485-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dissolving microneedles for enhanced local delivery of capsaicin to rat skin tissue.2017

    • Author(s)
      Ito Y, Kobuchi S, Inoue G, Kakumu E, Aoki M, Sakaeda T, Takada K.
    • Journal Title

      J Drug Target.

      Volume: 25 Issue: 5 Pages: 420-424

    • DOI

      10.1080/1061186x.2016.1266650

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dissolving Microneedles as Skin Allergy Test Device2017

    • Author(s)
      Ito Y, Matsumoto K, Osakama N, Yoshioka R, Kobuchi S, Sakaeda T, Takada K.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 4 Pages: 531-534

    • DOI

      10.1248/bpb.b16-00768

    • NAID

      130005530138

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Population pharmacokinetic-pharmacodynamic modeling of 5-fluorouracil for toxicities in rats2016

    • Author(s)
      Shinji Kobuchi, Yukako Ito, and Toshiyuki Sakaeda
    • Journal Title

      Eur. J. Drug Metab. Pharmacokinet.

      Volume: 印刷中 Issue: 4 Pages: 707-718

    • DOI

      10.1007/s13318-016-0389-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Population pharmacokinetic modelling and simulation of 5-fluorouracil incorporating a circadian rhythm in rats.2016

    • Author(s)
      Kobuchi S, Ito Y, Nakano Y, and Sakaeda T.
    • Journal Title

      Xenobiotica

      Volume: 46 Issue: 7 Pages: 597-604

    • DOI

      10.3109/00498254.2015.1100767

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Five years molecular remission with an increase of WT1-specific CTLs after cessation of WT1 peptide vaccination in a patient with CML.2016

    • Author(s)
      Narita M, Masuko M, Takahashi M
    • Journal Title

      Int J Med Sci

      Volume: 13 Issue: 4 Pages: 0-0

    • DOI

      10.7150/ijms.13601

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of a bolus injection of 5-fluorouracil on dihydropyrimidine dehydrogenase activity in rats receiving continuous infusion of 5-fluorouracil.2016

    • Author(s)
      Shinji Kobuchi, Asuka Hayashi, Mayu Taniguchi, Yukako Ito, Takao Tamura and Toshiyuki Sakaeda
    • Journal Title

      Cancer Chemother. Pharmacol.,

      Volume: 78 Issue: 3 Pages: 517-523

    • DOI

      10.1007/s00280-016-3105-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Population pharmacokinetic-pharmacodynamic (PK-PD) modeling of 5-fluorouracil (5-FU) for myelosuppression in rats: predicting the whole time course of alterations of blood cell counts after the administration of various doses of 5-FU2015

    • Author(s)
      Yukako Ito, Shinji Kobuchi, Taro Hayakawa, Asako Nishimura, Nobuhito Shibata, and Toshiyuki Sakaeda:
    • Journal Title

      Drug Metab. Rev

      Volume: 47(S1) Pages: 239-239

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Semi-physiological pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation of 5-fluorouracil for thrombocytopenia in rats.2015

    • Author(s)
      1)Shinji Kobuchi, Yukako Ito, Taro Hayakawa, Asako Nishimura, Nobuhito Shibata, Kanji Takada, and Toshiyuki Sakaeda:
    • Journal Title

      Xenobiotica

      Volume: 45 Pages: 19-28

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] オキサリプラチン投与による骨髄抑制発現と体内動態の関連性2017

    • Author(s)
      勝山陽介, 清水理紗, 河渕真治, 伊藤由佳子, 栄田敏之
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 大腸癌モデルラットにおけるオキサリプラチンの体内動態と蓄積性末梢神経障害の評価2017

    • Author(s)
      武貞和希,清水理紗,高橋千春,武田茉子,森本実希,河渕真治,伊藤由佳子,栄田敏之
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 大腸癌モデルラットにおける UFT 反復投与後の体内動態と治療効果との関係性2017

    • Author(s)
      津田基, 岡村真生, 中村貴憲, 河渕真治, 伊藤由佳子, 栄田敏之
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 5FU代謝酵素に着目した膵癌におけるFOLFIRINOX治療効果予測因子に関する検討.2017

    • Author(s)
      堀口 繁、伊藤由佳子、岡田 裕之
    • Organizer
      第103回日本消化器病学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腸がん化学療法における5-フルオロウラシルの血漿中濃度維持に及ぼすイリノテカンの影響.2017

    • Author(s)
      西尾夏美、河渕真治、伊藤由佳子、栄田敏之
    • Organizer
      日本薬剤学会第32年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Preclinical and clinical studies on establishment of invasive marker of dihydropyrimidine dehydrogenase activity and its usefulness in 5-fluorouracil-based chemotherapy.2017

    • Author(s)
      Yukako Ito, Shinji Kobuchi, Shigeru Horiguchi, Hironari Kato, Hidenori Shiraha, Toshiyuki Sakaeda
    • Organizer
      15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Population pharmacokinetic-pharmacodynamic model of 5-fluorouracil for evaluation of myelosuppression and body weight loss.2017

    • Author(s)
      Shinji Kobuchi, Yukako Ito, Toshiyuki Sakaeda
    • Organizer
      15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tumoral distribution of tegafur and 5-fluorouracil after UFT administration to colorectal cancer rats.2017

    • Author(s)
      Takanori Nakamura, Shinji Kobuchi, Yukako Ito, and Toshiyuki Sakaeda
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] イリノテカンの骨髄抑制に関する薬物動態学的/毒性薬力学的評価2017

    • Author(s)
      森賢也、西尾夏美、河渕真治、伊藤由佳子、栄田敏之
    • Organizer
      第67回日本薬学会近畿支部総会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] オキサリプラチン誘発蓄積性末梢神経障害の発現予測に関する血漿中オキサリプラチン濃度と総白金濃度との比較2017

    • Author(s)
      武田茉子、武貞和希、河渕真治、伊藤由佳子、栄田敏之
    • Organizer
      第27回日本医療薬学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Pharmacokinetics and toxicodynamics of oxaliplatin-induced peripheral neuropathy in colorectal cancer model rats.2017

    • Author(s)
      Waki Takesada, Mako Takeda, Miki Morimoto, Shinji Kobuchi, Yukako Ito, Toshiyuki Sakaeda
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Pharmacokinetic-pharmacodynamic modeling of oxaliplatin for hematological toxicity in rats.2017

    • Author(s)
      Yosuke Katsuyama, Shinji Kobuchi, Yukako Ito, Toshiyuki Sakaeda
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation of UFT on multiple dosing in colorectal cancer rats.2017

    • Author(s)
      Motoi Tsuda, Maki Okamura, Takanori Nakamura, Shinji Kobuchi, Yukako Ito, Toshiyuki Sakaeda
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 大腸がんモデルラットにおけるオキサリプラチン反復投与後の抗腫瘍効果に関する薬物動態学的/薬力学的評価.2017

    • Author(s)
      高橋千春、河渕真治、伊藤由佳子、栄田敏之:
    • Organizer
      第38回日本臨床薬理学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 癌化学療法における細胞間質液モニタリングの有用性に関する検討2017

    • Author(s)
      徳永寛人, 鶴田弘明, 河渕真治, 伊藤 由佳子, 栄田 敏之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] FOLFIRINOX療法における抗癌剤の体内動態とバイオマーカーに関する検討2017

    • Author(s)
      森わかな, 伊藤由佳子, 河渕真治, 栄田敏之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膵癌化学療法における治療選択バイオマーカーに関する検討2017

    • Author(s)
      柄田佐和子, 伊藤由佳子, 河渕真治, 堀口繁, 加藤博也, 白羽英則, 栄田敏之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 大腸癌モデルラットにおけるオキサリプラチン誘発急性末梢神経障害と血漿中薬 物濃度に関する基礎的検討2017

    • Author(s)
      森本実希, 武貞和希, 高橋千春, 武田茉子, 河渕真治, 伊藤由佳子, 栄田敏之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腎障害時のオキサリプラチン体内動態に関する検討2017

    • Author(s)
      甲斐美優, 古家真優, 河渕真治, 伊藤由佳子, 栄田敏之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腎障害モデルラットにおける TS-1 の体内動態に関する基礎的検討2017

    • Author(s)
      古家真優, 甲斐美優, 河渕真治, 伊藤由佳子, 栄田 敏之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TS-1 反復投与後の体内動態と DPD 活性に関する基礎的検討2017

    • Author(s)
      田野遥, 河渕真治, 伊藤由佳子, 栄田敏之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 母集団薬物動態解析によるカペシタビン投与後の5-fluorouracilの日内変動把握.2016

    • Author(s)
      矢崎由希子、河渕真治、伊藤由佳子、栄田敏之:
    • Organizer
      第37回日本臨床薬理学会学術総会
    • Place of Presentation
      米子
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
  • [Presentation] Population pharmacokinetic analysis of capecitabine for circadian variations in rats.2016

    • Author(s)
      Yukiko Yazaki, Shinji Kobuchi, Yukako Ito and Toshiyuki Sakaeda:
    • Organizer
      日本薬物動態学会第31回年会
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] umoral distribution of capecitabine and 5-fluorouracil after capecitabine administration to colorectal cancer rats.2016

    • Author(s)
      Yusuke Nose, Takakazu Sato, Shinji Kobuchi, Yukako Ito and Toshiyuki Sakaeda:
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] オキサリプラチン誘発末梢神経障害の発現リスクと血漿中体内動態との関連性2016

    • Author(s)
      清水理紗、高橋千春、武貞和希、武田茉子、森本実希、河渕真治、伊藤由佳子、栄田俊之
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜、神奈川
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] カペシタビン反復投与後のカペシタビンの体内動態及び腫瘍内濃度の変動.2016

    • Author(s)
      佐藤孝和、能勢祐輔、河渕真治、伊藤由佳子、栄田敏之:
    • Organizer
      第1回日本臨床薬理学会近畿地方会
    • Place of Presentation
      大阪
    • Related Report
      2016 Research-status Report
  • [Presentation] Capecitabineの体内動態に及ぼす5-fluorouracil先行急速静脈内投与の影響.2016

    • Author(s)
      芥川真子、河渕真治、伊藤由佳子、栄田敏之:
    • Organizer
      第66回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪
    • Related Report
      2016 Research-status Report
  • [Presentation] 5-fluorouracilの急速静脈内投与によるdihydropyrimidine dehydrogenase活性への影響2015

    • Author(s)
      林明日香、谷口真優、河渕真治、伊藤由佳子、田村孝雄、栄田敏之:
    • Organizer
      . 第36回日本臨床薬理学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2015-12-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Pharmacokinetic alterations of capecitabine and 5-fluorouracil after repeated administration of capecitabine to rats with colorectal cancer.2015

    • Author(s)
      Takakazu Sato, Kota Shinohara, Shinji Kobuchi, Yukako Ito, Toshiyuki Sakaeda:
    • Organizer
      日本薬物動態学会第30回年会
    • Place of Presentation
      東京
    • Year and Date
      2015-11-12
    • Related Report
      2015 Research-status Report
  • [Presentation] Increase in steady-state plasma concentrations of 5-fluorouracil (5-FU) via the suppression of dihydropyrimidine dehydrogenase activity by a bolus injection of 5-FU in advance.2015

    • Author(s)
      Shinji Kobuchi, Yukako Ito, Takao Tamura, and Toshiyuki Sakaeda:
    • Organizer
      14th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology
    • Place of Presentation
      Rotterdam, Netherlands
    • Year and Date
      2015-10-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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