Individualized molecular targeted therapy based on pharmacogenomics and pharmacokinetic optimization

• Project/Area Number: 23790597
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Kyoto University
• Principal Investigator: FUKUDO Masahide 京都大学, 医学研究科, 助教 (60437233)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 分子標的治療薬 / 薬物動態 / 有効性 / 安全性 / ゲノム情報 / 個別最適投与 / 薬理ゲノム / 個別最適化 / 副作用 / 個別化投与設計

Research Abstract

We demonstrated that plasma concentration of sorafenib was significantly higher in patients with renal cell carcinoma or hepatocellular carcinoma who developed grade 2 or higher hand-foot skin reaction as compared with those without the adverse event. Furthermore, the cumulative incidence of grade 3/4 adverse events was closely related with early drug exposure in lung cancer patients treated with erlotinib. These findings suggest that drug concentrations could be a useful predictor for avoiding adverse events induced by molecular targeted agents.

Research Products

• [Journal Article] Population pharmacokinetics/pharmacodynamics of erlotinib and pharmacogenomic analysis of plasma and cerebrospinal fluid drug concentrations in Japanese patients with non-small cell lung cancer. (2013)
  • Author(s): Fukudo M, Ikemi Y, Togashi Y, Masago K, Kim YH, Mio T, Terada T, Teramukai S, Mishima M, Inui K, Katsura T.
  • Journal Title: Clinical Pharmacokinetics Volume: 52 Issue: 7 Pages: 593-609
  • DOI: 10.1007/s40262-013-0058-5
  • Peer Reviewed
• [Journal Article] Impact of Genetic Variation in Breast Cancer Resistance Protein (<i>BCRP</i>/<i>ABCG2</i>) on Sunitinib Pharmacokinetics (2012)
  • Author(s): Tomoyuki Mizuno
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 27 Issue: 6 Pages: 631-639
  • DOI: 10.2133/dmpk.DMPK-12-RG-026
  • NAID: 130004933515
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed
• [Journal Article] Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer (2012)
  • Author(s): Yosuke Togashi
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 70 Issue: 3 Pages: 399-405
  • DOI: 10.1007/s00280-012-1929-4
  • Peer Reviewed
• [Journal Article] Plasma and pleural fluid pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small-cell lung cancer with pleural effusion (2011)
  • Author(s): Masago, K., Togashi, Y., Fukudo, M., Terada, T.
  • Journal Title: Clin. Lung Cancer Volume: 12(5) Issue: 5 Pages: 307-312
  • DOI: 10.1016/j.cllc.2011.06.004
  • Peer Reviewed
• [Journal Article] Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation (2011)
  • Author(s): Togashi Y, et al
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 68 Issue: 4 Pages: 1089-1092
  • DOI: 10.1007/s00280-011-1691-z
  • Peer Reviewed
• [Presentation] スニチニブの体内動態に及ぼすABCB1、ABCG2 阻害の影響 (2012)
  • Author(s): 國松佐千子、水野知行、福土将秀、桂 敏也、松原和夫.
  • Organizer: 第62回日本薬学会近畿支部総会・大会
  • Place of Presentation: 兵 庫 県西宮
  • Year and Date: 2012-10-20
• [Presentation] 腎細胞がんおよび肝細胞がん患者におけるソラフェニブの母集団薬物動態解析 (2012)
  • Author(s): 水野知行、福土将秀、寺田智祐、國松佐千子、新迫恵子、津田真弘、波多野悦朗、上本伸二、神波大己、中村英二郎、小川 修、妹尾 浩、千葉 勉、乾 賢一、桂 敏也
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸
• [Presentation] 腎細胞がんおよび肝細胞がん患者におけるソラフェニブの母集団薬物動態解析 (2012)
  • Author(s): 水野知行
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Population pharmacokinetics and pharmacogenomics of erlotinib: Impact of drug exposure on treatment outcomes in Japanese patients with non-small cell lung cancer (2011)
  • Author(s): Fukudo M, Ikemi Y, Togashi Y, Masago K, Kim YH, Mio T, Mishima M, Inui K, Katsura T.
  • Organizer: 2011 ASCO Annual Meeting
  • Place of Presentation: Chicago, IL, USA
• [Presentation] 進行肝細胞がん患者におけるソラフェニブの服薬継続並びに有害事象発現に関する要因解析 (2011)
  • Author(s): 福土将秀、下雅意 彩、深津祥央、矢野育子、桂 敏也
  • Organizer: 第5回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 名古屋
• [Presentation] 進行肝細胞がん患者におけるソラフェニブの服薬継続並びに有害事象発現に及ぼす影響因子の検討. (2011)
  • Author(s): 下雅意 彩、福土将秀、深津祥央、矢野育子、桂 敏也.
  • Organizer: 第21回日本医療薬学会年会
  • Place of Presentation: 神戸
• [Presentation] エルロチニブの母集団薬物動態と副作用に関する薬理ゲノム解析 (2011)
  • Author(s): 福土将秀、池見泰明 、冨樫庸介 、真砂勝泰 、金 永学、三嶋理晃、桂 敏也
  • Organizer: 第32回日本臨床薬理学会年会
  • Place of Presentation: 浜松
• [Presentation] Role of ABCG2 and ABCB1 in sunitinib pharmacokinetics. (2011)
  • Author(s): Mizuno T, Fukudo M, Katsura T.
  • Organizer: 26thJSSX Annual Meeting
  • Place of Presentation: Hiroshima
• [Presentation] エルロチニブの母集団薬物動態と副作用に関する薬理ゲノム解析 (2011)
  • Author(s): 福土将秀
  • Organizer: 第32回日本臨床薬理学会年会
  • Place of Presentation: アクトシティ浜松（浜松市）
• [Presentation] Investigation of factors influencing treatment continuation with sorafenib and the development of adverse events in patients with advanced hepatocellular carcinoma (2011)
  • Author(s): Fukudo M
  • Organizer: 第5回若手医療薬科学シンポジウム
  • Place of Presentation: 名古屋大学医学部附属病院（名古屋市）
• [Presentation] Role of ABCG2 and ABCB1 in sunitinib pharmacokinetics (2011)
  • Author(s): Mizuno T
  • Organizer: 日本薬物動態学会第26回年会
  • Place of Presentation: 広島国際会議場（広島市）
• [Presentation] 進行肝細胞がん患者におけるソラフェニブの服薬継続並びに有害事象発現に及ぼす影響因子の検討 (2011)
  • Author(s): 下雅意 彩
  • Organizer: 第21回日本医療薬学会年会
  • Place of Presentation: 神戸国際展示場ほか（神戸市）
• [Presentation] Population pharmacokinetics and pharmacogenomics of erlotinib: Effect of drug exposure on treatment outcomes in Japanese patients with non-small cell lung cancer (2011)
  • Author(s): Fukudo M
  • Organizer: 第47回米国臨床腫瘍学会総会（2011 ASCO Annual Meeting）
  • Place of Presentation: マコーミックプレイス（シカゴ市、アメリカ）
• [Presentation] スニチニブの体内動態に及ぼすABCB1、ABCG2 阻害の影響
  • Author(s): 國松佐千子
  • Organizer: 第62回日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
• [Remarks] ホームページ
  • URL: http://www.kuhp.kyoto-u.ac.jp/~yakuzai/main.htm
• [Remarks] 京都大学医学部附属病院薬剤部
  • URL: http://www.kuhp.kyoto-u.ac.jp/~yakuzai/main.htm
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~yakuzai/main.htm