Establishment of photosafety testing tools on the basis of physicochemical and biopharmaceutical data

• Project/Area Number: 17K08453
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: Onoue Satomi 静岡県立大学, 薬学部, 教授 (00457912)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 光線過敏症 / 創薬 / 安全性 / 光化学 / 薬剤反応性 / 光毒性 / 副作用

Outline of Final Research Achievements

To establish the reliable photosafety testing approach, model chemicals were subjected to photochemical, photobiochemical and pharmacokinetic characterization. Upon these data, photosafety testing tools were proposed with combination use of reactive oxygen species (ROS) assay and pharmacokinetic analysis. Preliminary validation testing was carried out for the proposed apporoach, and the ROS assay was successfully adopted as OECD test guideline 495 in 2019.

Academic Significance and Societal Importance of the Research Achievements

これまで現象論で捉えられる傾向にあった薬剤性光線過敏症の発症機序をはじめて統合的に理解することができ，さらに未だ確実な評価系に欠ける光安全性評価を可能となった．また，開発した試験法を多くの化合物に適用してデータを蓄積することで，各種光毒性反応を誘発しやすい化合物の構造上ならびに物性上の特性が明らかとなる．それによって各種光毒性反応に関する structural alert を新たに提示でき，医薬品・化粧品・食品をはじめとする新規化学物質の創製において極めて有用な情報を世界に向けて共有可能となるであろう．

Research Products

• [Journal Article] Phototoxic risk assessment of dermally-applied chemicals with structural variety based on photoreactivity and skin deposition (2020)
  • Author(s): Seto Yoshiki、Ohtake Hiroto、Sato Hideyuki、Onoue Satomi
  • Journal Title: Regulatory Toxicology and Pharmacology Volume: 113 Pages: 104619-104619
  • DOI: 10.1016/j.yrtph.2020.104619
  • Peer Reviewed
• [Journal Article] Strategic photosafety screening system consisting of in chemico photoreactivity and in vitro skin exposure for quinolone derivatives. (2020)
  • Author(s): Iyama Y, Sato H, Seto Y, Onoue S
  • Journal Title: Eur J Pharm Sci. Volume: 146 Pages: 105257-105257
  • DOI: 10.1016/j.ejps.2020.105257
  • Peer Reviewed
• [Journal Article] A new photosafety screening strategy based on in chemico photoreactivity and in vitro skin exposure for dermally-applied chemicals (2019)
  • Author(s): Iyama Y, Sato H, Seto Y, Onoue S
  • Journal Title: Toxicol Lett. Volume: 317 Pages: 45-52
  • DOI: 10.1016/j.toxlet.2019.09.016
  • Peer Reviewed
• [Journal Article] Photochemical and Pharmacokinetic Characterization of Orally Administered Chemicals to Evaluate Phototoxic Risk (2018)
  • Author(s): Yosuke Iyama, Hideyuki Sato, Yoshiki Seto, Satomi Onoue
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 108 Issue: 3 Pages: 1303-1308
  • DOI: 10.1016/j.xphs.2018.10.013
  • Peer Reviewed
• [Journal Article] Enhanced biopharmaceutical effects of tranilast on experimental colitis model with use of self-micellizing solid dispersion technology (2018)
  • Author(s): Kojo Y, Suzuki H, Kato K, Kaneko Y, Yuminoki K, Hashimoto N, Sato H, Seto Y, Onoue S
  • Journal Title: Int J Pharm Volume: 545 Issue: 1-2 Pages: 19-26
  • DOI: 10.1016/j.ijpharm.2018.04.053
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Avoidance of food effect on oral absorption profile of itraconazole by self-micellizing solid dispersion approach (2017)
  • Author(s): Kojo Y, Kobayashi K, Matsunaga S, Suzuki H, Seto Y, Sato H, Onoue S
  • Journal Title: Drug Metab Pharmacokinet Volume: 32 Issue: 5 Pages: 273-276
  • DOI: 10.1016/j.dmpk.2017.06.001
  • NAID: 210000170142
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Enzymatic reactive oxygen species assay to evaluate phototoxic risk of metabolites (2017)
  • Author(s): Kato M, Ohtake H, Sato H, Seto Y, Onoue S
  • Journal Title: Toxicol Lett Volume: 15 Pages: 59-65
  • DOI: 10.1016/j.toxlet.2017.07.852
  • Peer Reviewed / Int'l Joint Research
• [Presentation] in vivo 試験に依存しない光安全性予測：NSAIDs の光反応性および皮膚暴露量を指標として (2019)
  • Author(s): 徳吉泰春、猪山洋輔、佐藤秀行、世戸孝樹、尾上誠良
  • Organizer: 日本薬剤学会第 34 年会 (富山)
• [Presentation] 光安全性評価における光毒性代謝物の皮膚曝露とその推移の重要性：imipramine をモデルとした検討 (2019)
  • Author(s): 世戸孝樹、當波諒、猪山陽輔、佐藤秀行、尾上誠良
  • Organizer: 第 46 回日本毒性学会学術年会（徳島）
• [Presentation] Reactive oxygen species assay および in vitro 皮膚透過性試験を用いたキノロン系抗菌薬の光安全性評価 (2019)
  • Author(s): 猪山陽輔、佐藤秀行、世戸孝樹、尾上誠良
  • Organizer: 第 5 回日本医薬品安全性学会学術大会 （東京）
• [Presentation] 光反応性および in vitro 皮膚蓄積性の統合的解析による光安全性評価 (2019)
  • Author(s): 猪山陽輔、佐藤秀行、世戸孝樹、尾上誠良
  • Organizer: 第 25 回創剤フォーラム若手研究会 （千葉）
• [Presentation] Photosafety testing: the combination use of photoreactivity and skin deposition (2019)
  • Author(s): Yosuke Iyama, Hideyuki Sato, Yoshiki Seto, Satomi Onoue
  • Organizer: 4th AFPS, Bali
• [Presentation] In vivo 実験に依存しない光化学的および in vitro 皮膚曝露評価に基づく光安全性評価系の開発 (2018)
  • Author(s): 猪山陽輔，佐藤秀行，世戸孝樹，尾上誠良
  • Organizer: 日本動物実験代替法学会 第 31 回大会 (熊本)
• [Presentation] A new in vitro photosafety screening system by combined use of photoreactivity and skin exposure of chemicals as an alternative to animal experiments (2018)
  • Author(s): Yosuke Iyama, Hideyuki Sato, Yoshiki Seto, Satomi Onoue
  • Organizer: merican Association of Pharmaceutical Scientists PharmSci 360
• [Presentation] Reactive oxygen species assay および in vitro 皮膚透過性試験を用いた新規光安全性評価系の開発 (2018)
  • Author(s): 猪山陽輔，佐藤秀行，世戸孝樹，尾上誠良
  • Organizer: 第 4 回 日本医薬品安全性学会学術大会 (岡山)
• [Presentation] 光反応性および皮膚内動態に基づく光安全性評価における動物実験代替法の開発 (2018)
  • Author(s): 猪山陽輔、佐藤秀行、世戸孝樹、尾上誠良
  • Organizer: 日本薬剤学会 第 33 回年会 (静岡)
• [Presentation] 光毒性リスクを回避する医薬品安全性試験法：基礎からレギュレーションまで (2017)
  • Author(s): 尾上誠良
  • Organizer: 平成28年度 薬学生涯研修講座
  • Invited
• [Presentation] 光化学的および薬物動態学的特性に基づく経口投与化合物の光安全性評価 (2017)
  • Author(s): 猪山陽輔、佐藤秀行、世戸孝樹、尾上誠良
  • Organizer: 日本薬剤学会 第 32 年会
• [Presentation] 光化学的および薬物動態学的特性の統合的解析による経口投与化合物の高効率的な光安全性評価 (2017)
  • Author(s): 猪山陽輔、加藤尚視、井上 僚、佐藤秀行、世戸孝樹、尾上誠良
  • Organizer: 第 44 回 日本毒性学会学術年会