Evaluation for change in drug distribution under hypothermia for optimization of medication

• Project/Area Number: 26860108
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Nagasaki University
• Principal Investigator: MIYAMOTO Hirotaka 長崎大学, 医歯薬学総合研究科(薬学系), 助教 (20619481)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 低体温療法 / CYP3A2 / タンパク結合 / 組織移行

Outline of Final Research Achievements

We have evaluated the pharmacokinetics of midazolam in rats under hypothermia. The plasma concentration of midazolam was increased under hypothermia. However, brain and liver concentration of midazolam did not change under hypothermia. This result suggest the distribution of midazolam was inhibited under hypothermia. We evaluated the protein binding of midazolam in rat serum. The free fraction of midazolam was significantly decreased compared to normal condition.

Research Products

• [Journal Article] Effect of Metabolic Inhibitors on the Hepatic Disposition of 5-Fluorouracil after Application to the Rat Liver Surface (2016)
  • Author(s): Kenta Shimokawa, Kazumi Wakasugi, Rei Tomonaga, Ken Utsunomiya, Hirotaka Miyamoto, Shintaro Fumoto, Koyo Nishida
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 39 Issue: 3 Pages: 361-367
  • DOI: 10.1248/bpb.b15-00757
  • NAID: 130005132312
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Establishment of the method for estimation the absorbed rate constant from the pharmacokinetic parameters obtained by package insert (2015)
  • Author(s): Hirotaka Miyamoto, Takenori Tsukinuki, Mariko Taniguchi, Eriko Kinoshita, Shintaro Fumoto, and Koyo Nishida
  • Organizer: 日本薬物動態学会第30年会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-11-12
• [Presentation] Development of two-layer sheet formulation containing 5-FU and its pharmacokinetic consideration after application to rat liver surface (2015)
  • Author(s): Koyo Nishida, Yosuke Kariya, Ken Utsunomiya Yoshimi Tsurusaki, Kenta Shimokawa, Hirotaka Miyamoto, Shintaro Fumoto
  • Organizer: 日本薬物動態学会第30年会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-11-12
• [Presentation] 生理学的薬物速度論による低体温時のラットにおけるミダゾラム体内動態の予測 (2015)
  • Author(s): 宮元敬天、森塚暁裕、谷口麻里子、麓伸太郎、西田孝洋
  • Organizer: 第18回日本脳低温療法学会
  • Place of Presentation: 香川県民ホール（香川県高松市）
  • Year and Date: 2015-07-10
• [Presentation] 急性肝炎モデルラットにおけるmidaaolzmの体内動態および変動要因の解析 (2015)
  • Author(s): 谷口 麻里子、宮元 敬天、平田 春奈、麓 伸太郎、西田 孝洋
  • Organizer: 日本薬剤学会第30年会
  • Place of Presentation: 長崎ブリックホール（長崎県長崎市）
  • Year and Date: 2015-05-21
• [Presentation] EVALUATION FOR CHANGE IN THE DISPOSITION OF MIDAZOLAM UNDER HYPOTHERMIA IN RATS BY IN VITRO METABOLISM AND PROTEIN BINDING STUDY (2014)
  • Author(s): Hirotaka Miyamoto, Mariko Taniguchi, Haruna Hirata, Shintaro Fumoto and Koyo Nishida
  • Organizer: 29th JSSX Meeting and 19th North American ISSX Meeting
  • Place of Presentation: Hilton San Francisco Union Square（アメリカ）
  • Year and Date: 2014-10-19 – 2014-10-23
• [Presentation] 肝クリアランスの予測に基づく低体温時におけるミダゾラム定速注入時の投与速度最適化 (2014)
  • Author(s): 宮元 敬天、松枝 慧、森塚 暁裕、堀 友理香、麓 伸太郎、西田 孝洋
  • Organizer: 第17回日本脳低温療法学会
  • Place of Presentation: プラザ ヴェルデ（静岡県沼津市）
  • Year and Date: 2014-08-01 – 2014-08-02
• [Presentation] HepG2細胞における活発なエンドサイトーシス経路と細胞周期の関連 (2014)
  • Author(s): 宇根隆通、麓伸太郎、宮元敬天、西田孝洋
  • Organizer: 第30回日本DDS学会学術集会
  • Place of Presentation: 慶應義塾大学 薬学部 芝共立キャンパス（東京都港区）
  • Year and Date: 2014-07-30 – 2014-07-31
• [Presentation] 添付文書記載の薬物動態パラメータを用いたExcel VBAによる吸収速度定数の推定 (2014)
  • Author(s): 西田孝洋、突貫雄紀、平田春奈、下川研太、宮元敬天
  • Organizer: 医療薬学フォーラム
  • Place of Presentation: ビッグサイトTFTホール（東京都江東区）
  • Year and Date: 2014-06-28 – 2014-06-29
• [Remarks] 研究業績
  • URL: http://www.ph.nagasaki-u.ac.jp/lab/dds/res/paper.html
• [Remarks] 学会発表
  • URL: http://www.ph.nagasaki-u.ac.jp/lab/dds/res/meeting.html
• [Remarks] 長崎大学薬学部薬剤学研究室
  • URL: http://www.ph.nagasaki-u.ac.jp/lab/dds/index-j.html