Usefulness of Pharmacogenomics in Clinical Practice

• Project/Area Number: 17K15504
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Ritsumeikan University
• Principal Investigator: Hira Daiki 立命館大学, 薬学部, 助教 (50636959)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 個別医療 / 遺伝子多型解析 / 医療薬学 / 遺伝子検査 / 疼痛管理

Outline of Final Research Achievements

In this study, the impact of the CYP2D6 polymorphism on the effect of Tramadol was evaluated to explain the individual difference in analgesic.
There are few genetic variants in which the activity of CYP2D6 is extremely decreased in Japanese people. However, even genetic polymorphisms in which the activity of CYP2D6 is slightly decreased, which, which are frequently observed in Japanese, significantly affect the efficacy of Tramadol.

Academic Significance and Societal Importance of the Research Achievements

本研究では、薬物の効果の個人差を遺伝子変異の有無により説明することを目的としている。遺伝子変異の評価に基づいて個々の患者さんに合わせた薬剤選択や投与量決定が可能となれば、(1) いち早く最適な治療効果が達成できることによる治療効率の向上や、(2) 過剰投与が防止できることによる副作用頻度の低下という医学的なメリットに加え、(3) 投与量の最適化による薬剤費の負担軽減や、(4) 副作用頻度の低減による副作用の治療のための医療費の軽減など、経済学的なメリットが期待できる。

Research Products

• [Journal Article] Is “Slow Inhalation” Always Suitable for Pressurized Metered Dose Inhaler? (2020)
  • Author(s): Hira Daiki, Okuda Tomoyuki, Mizutani Ayano, Tomida Nao, Mizuno Megumi, Ueshima Satoshi, Kakumoto Mikio, Okano Tomonobu, Okamoto Hirokazu
  • Journal Title: AAPS PharmSciTech Volume: 21 Issue: 2 Pages: 53-53
  • DOI: 10.1208/s12249-019-1610-x
  • Peer Reviewed
• [Journal Article] 薬学的視点に基づいたプレシジョン・メディシンの国内基盤構築のための調査研究 (2020)
  • Author(s): 辻 大樹、斎藤嘉朗、莚田泰誠、三浦昌朋、平 大樹、寺田智祐
  • Journal Title: 医療薬学 Volume: 46 Pages: 66-76
  • NAID: 130007983444
  • Peer Reviewed
• [Journal Article] Genetic variants of alcohol‐metabolizing enzymes in Brugada syndrome: Insights into syncope after drinking alcohol (2019)
  • Author(s): Wu Qi、Hayashi Hideki、Hira Daiki、Sonoda Keiko、Ueshima Satoshi、Ohno Seiko、Makiyama Takeru、Terada Tomohiro、Katsura Toshiya、Miura Katsuyuki、Horie Minoru
  • Journal Title: Journal of Arrhythmia Volume: 35 Issue: 5 Pages: 752-759
  • DOI: 10.1002/joa3.12227
  • NAID: 120006848263
  • Peer Reviewed / Open Access
• [Journal Article] Population pharmacokinetics and pharmacodynamics of apixaban linking its plasma concentration to intrinsic activated coagulation factor X activity in Japanese patients with atrial fibrillation (2019)
  • Author(s): Ueshima Satoshi、Hira Daiki、Tomitsuka Chiho、Nomura Miki、Kimura Yuuma、Yamane Takuya、Tabuchi Yohei、Ozawa Tomoya、Itoh Hideki、Horie Minoru、Terada Tomohiro、Katsura Toshiya
  • Journal Title: The AAPS Journal Volume: 21 Issue: 5 Pages: 80-80
  • DOI: 10.1208/s12248-019-0353-7
  • Peer Reviewed / Open Access
• [Journal Article] Exploratory Investigation of Target Pazopanib Concentration Range for Patients With Renal Cell Carcinoma (2019)
  • Author(s): Satoshi Noda, Tetsuya Yoshida, Daiki Hira, Ryosuke Murai, Keiji Tomita, Teruhiko Tsuru, Susumu Kageyama, Akihiro Kawauchi, Yoshito Ikeda, Shin-ya Morita, Tomohiro Terada.
  • Journal Title: Clinical Genitourinary Cancer Volume: 17 Issue: 2 Pages: e306-e313
  • DOI: 10.1016/j.clgc.2018.12.001
  • Peer Reviewed
• [Journal Article] Low Body Mass Index and Myeloablative Conditioning Regimen Prolong the Duration of Parenteral Nutrition During Hematopoietic Stem Cell Transplantation (2019)
  • Author(s): Kamiya Takaki、Hira Daiki、Hoshino Nobuo、Kurihara Mika、Nakagawa Mayumi、Sasaki Masaya、Terada Tomohiro
  • Journal Title: Annals of Nutrition and Metabolism Volume: 74 Issue: 2 Pages: 107-114
  • DOI: 10.1159/000496457
  • Peer Reviewed
• [Journal Article] Systematic review of salivary versus blood concentrations of antituberculosis drugs and their potential for salivary therapeutic drug monitoring. (2018)
  • Author(s): van den Elsen Simone H.J.、Oostenbrink Lisette M.、Heysell Scott K.、Hira Daiki、Touw Daan J.、Akkerman Onno W.、Bolhuis Mathieu S.、Alffenaar Jan-Willem C.
  • Journal Title: Therapeutic Drug Monitoring Volume: 40 Issue: 1 Pages: 17-37
  • DOI: 10.1097/ftd.0000000000000462
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] In-vitro evaluation of optimal inhalation flow patterns for commercial dry powder inhalers and pressurized metered dose inhalers with human inhalation flow pattern simulator (2018)
  • Author(s): Hira Daiki、Okuda Tomoyuki、Mizutani Ayano、Tomida Nao、Okamoto Hirokazu
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 107 Issue: 6 Pages: 1731-1735
  • DOI: 10.1016/j.xphs.2018.02.002
  • Peer Reviewed
• [Journal Article] Assessment of inhalation flow patterns of soft mist inhaler co-prescribed with dry powder inhaler using inspiratory flow meter for multi inhalation devices (2018)
  • Author(s): Hira Daiki、Koide Hiroyoshi、Nakamura Shigemi、Okada Toyoko、Ishizeki Kazunori、Yamaguchi Masafumi、Koshiyama Setsuko、Oguma Tetsuya、Ito Kayoko、Funayama Saori、Komase Yuko、Morita Shin-ya、Nishiguchi Kohshi、Nakano Yasutaka、Terada Tomohiro
  • Journal Title: PLOS ONE Volume: 13 Issue: 2 Pages: e0193082-e0193082
  • DOI: 10.1371/journal.pone.0193082
  • Peer Reviewed / Open Access
• [Journal Article] Concomitant administration of candesartan cilexetil in patients on paclitaxel and carboplatin combination therapy increases risk of severe neutropenia (2018)
  • Author(s): Katsube Yurie、Hira Daiki、Tsujimoto Masayuki、Koide Hiroyoshi、Minegaki Tetsuya、Ikeda Yoshito、Morita Shin-ya、Nishiguchi Kohshi、Terada Tomohiro
  • Journal Title: Int. Journal of Clinical Pharmacology and Therapeutics Volume: 56 Issue: 07 Pages: 328-336
  • DOI: 10.5414/cp203180
  • Peer Reviewed
• [Journal Article] Effect of nasally exhaling budesonide/formoterol dry powder inhaled at “fast” inspiratory flow on eosinophilic chronic rhinosinusitis (2018)
  • Author(s): Hamada Satoshi、Hira Daiki、Kobayashi Yoshiki、Yasuba Hirotaka
  • Journal Title: Int. Journal of Clinical Pharmacology and Therapeutics Volume: 56 Issue: 11 Pages: 539-543
  • DOI: 10.5414/cp203272
  • Peer Reviewed
• [Journal Article] Pharmaceutical stability of colloidal saccharated iron oxide injection in normal saline (2018)
  • Author(s): Daiki Hira, Asami Suzuki, Yusuke Kono, Kosuke Shimokawa, Serika Matsuoka, Ken-yuh Hasumoto, Hiroyuki Kawahara, Masahide Onoue, Takuya Fujita, Tomonobu Okano and Mikio Kakumoto
  • Journal Title: J. Pharm. Health Care Sci. Volume: 4 Issue: 1 Pages: 1-6
  • DOI: 10.1186/s40780-018-0116-0
  • Peer Reviewed / Open Access
• [Journal Article] Oral mucositis associated with anti-EGFR therapy in colorectal cancer: single institutional retrospective cohort study (2018)
  • Author(s): Dote Satoshi、Itakura Shoji、Kamei Kohei、Hira Daiki、Noda Satoshi、Kobayashi Yuka、Terada Tomohiro
  • Journal Title: BMC Cancer Volume: 18 Issue: 1 Pages: 957-957
  • DOI: 10.1186/s12885-018-4862-z
  • Peer Reviewed / Open Access
• [Journal Article] BCRP/ABCG2 and high-alert medications: Biochemical, pharmacokinetic, pharmacogenetic, and clinical implications. (2018)
  • Author(s): Hira D, Terada T.
  • Journal Title: Biochem. Pharmacol. Volume: 147 Pages: 201-210
  • DOI: 10.1016/j.bcp.2017.10.004
  • Peer Reviewed
• [Journal Article] Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation. (2018)
  • Author(s): Ueshima S, Hira D, Kimura Y, Fujii R, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Ohno S, Horie M, Terada T, Katsura T.
  • Journal Title: Br. J. Clin. Pharmacol. Volume: - Issue: 6 Pages: 1301-1312
  • DOI: 10.1111/bcp.13561
  • Peer Reviewed / Open Access
• [Journal Article] Letter: CYP3A4/5 genotype status and outcome of vonoprazan-containing Helicobacter pylori eradication therapy in Japan. (2017)
  • Author(s): Sugimoto M, Ban H, Hira D, Kamiya T, Otsuka T, Inatomi O, Bamba S, Terada T, Andoh A.
  • Journal Title: Aliment Pharmacol Ther. Volume: 45 Issue: 7 Pages: 1009-1010
  • DOI: 10.1111/apt.13959
  • Peer Reviewed / Open Access
• [Journal Article] Impact of ABCB1, ABCG2, and CYP3A5 polymorphisms on plasma trough concentrations of apixaban in Japanese patients with atrial fibrillation (2017)
  • Author(s): Satoshi Ueshima, Daiki Hira, Ryo Fujii, Yuuma Kimura, Chiho Tomitsuka, Takuya Yamane, Yohei Tabuchi, Tomoya Ozawa, Hideki Itoh, Minoru Horie, Tomohiro Terada, Toshiya Katsura
  • Journal Title: Pharmacogenetics and Genomics Volume: 27 Issue: 9 Pages: 329-336
  • DOI: 10.1097/fpc.0000000000000294
  • Peer Reviewed
• [Presentation] 実臨床におけるファーマコゲノミクス検査の活用状況 (2019)
  • Author(s): 平 大樹、辻大樹、齋藤嘉朗、莚田泰誠、三浦昌朋、寺田智祐
  • Organizer: 第29回日本医療薬学会年会
  • Invited
• [Presentation] 日本人におけるトラマドールの鎮痛効果に及ぼすCYP2D6遺伝子型の影響 (2019)
  • Author(s): 篠田和葉、神谷貴樹、平 大樹、岩下成人、中島 亮、上島 智、角本幹夫、今井晋二、福井 聖、寺田智祐
  • Organizer: 第3回フレッシャーズ・カンファランス
• [Presentation] トラマドールの鎮痛効果におけるCYP2D6遺伝子多型測定の臨床的意義 (2019)
  • Author(s): 神谷貴樹、中島亮、平大樹、元持杏津子、森河内彩、篠田和葉、米田真悟、今井晋二、寺田智祐
  • Organizer: 第29回日本医療薬学会年会
• [Presentation] CYP2D6遺伝子型に応じた鎮痛薬トラマドールの個別投与法に関するレトロスペクティブ解析 (2019)
  • Author(s): 神谷貴樹、中島亮、平大樹、森河内彩、元持杏津子、篠田和葉、米田真悟、今井晋二、寺田智祐
  • Organizer: 第40回日本臨床薬理学会学術総会
• [Presentation] 薬物代謝酵素の遺伝子多型測定に基づくトラマドールの個別化投与設計 (2018)
  • Author(s): 平 大樹, 岩下成人, 神谷貴樹, 中島 亮, 磯野哲一郎, 赤羽理也, 池田義人, 角本幹夫, 森田真也, 岡野友信, 今井晋二, 福井 聖, 寺田智祐
  • Organizer: 第40回 日本疼痛学会
• [Presentation] ファーマコゲノミクス検査の臨床実装 (2018)
  • Author(s): 寺田 智祐, 平 大樹
  • Organizer: 第35回日本TDM学会学術大会
• [Presentation] ファーマコゲノミクス検査に基づいた抗血小板薬選択の実態調査（優秀発表賞受賞） (2018)
  • Author(s): 磯野哲一郎, 平 大樹, 福井里佳, 田淵陽平, 赤羽理也, 池田義人, 森田真也, 寺田智祐
  • Organizer: 第35回日本TDM学会学術大会
• [Presentation] トラマドールの個別化投与設計を目指したCYP2D6遺伝子多型測定体制の構築 (2017)
  • Author(s): 平 大樹, 岩下成人, 神谷貴樹, 中島 亮, 磯野哲一郎, 赤羽理也, 森田真也, 今井晋二, 福井 聖, 寺田智祐
  • Organizer: 第39回 日本疼痛学会
• [Presentation] Pharmacogenomics in Clinical Practice (2017)
  • Author(s): Daiki Hira, Tomohiro Terada
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Int'l Joint Research / Invited
• [Presentation] 実臨床における薬効・薬物動態評価のためのファーマコメトリクスの活用 (2017)
  • Author(s): 平 大樹, 寺田 智祐
  • Organizer: 第27回 日本医療薬学会年会
  • Invited