Examination for genomic biomarkers of intestinal and renal drug transporters aiming for the personalized medicine

• Project/Area Number: 23590646
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kitasato University
• Principal Investigator: FUJITA Tomoe 北里大学, 医学部, 講師 (20296510)
• Co-Investigator(Kenkyū-buntansha): MAJIMA Masataka 北里大学, 医学部, 教授 (70181641)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ガバペンチン / アミノ酸トランスポーター / 有機カチオントランスポーター / 一塩基多型（SNP） / 薬物動態 / 個別化薬物治療 / 薬物トランスポーター / LAT2 / OCTN1 / 小腸吸収 / 腎排泄 / 個別化治療 / SNP

Research Abstract

The study examined a type and frequency of single nucleotide polymorphisms (SNPs) of the drug transporters which may contribute to the inter-individual variability of pharmacokinetics of gabapentin in healthy Japanese volunteers. Regarding with the unknown SNP of L-type amino acid transporter 2 (LAT2), absorption of gabapentin increased in two subjects homozygous for the common allele, four subjects heterozygous and one subject homozygous for the mutant allele in this order. Frequency of these genotypes were 22, 45 and 22%, respectively in 73 Japanese. The unknown SNPs of organic cation transporter 1 (OCTN1) and multidrug and toxin extrusion protein 1 (MATE1) found in one subject whose renal excretion of gabapentin was low, were not detected in this population.

Research Products

• [Journal Article] Inhibitory effects of para-aminohippurate and probenecid on the renal clearance of adefovir and benzylpenicillin as probe drugs for organic anion transporter (OAT) 1 and OAT3 in humans. (2014)
  • Author(s): Maeda K, Tian Y, Fujita T, Ikeda Y, Kumagai Y, Kondo T, Tanabe K, Nakayama H, Horita S, Kusuhara H, Sugiyama Y.
  • Journal Title: Eur J Pharm Sci Volume: - Pages: 94-103
  • DOI: 10.1016/j.ejps.2014.04.004
  • Peer Reviewed / Open Access
• [Journal Article] Pharmacokinetics of teriparatide after subcutaneous administration to volunteers with renal failure: a pilot study. (2014)
  • Author(s): Imai H, Watanabe M, Fujita T, Watanabe H, Harada K, Moritoyo T; ANTCliPh (Academic Network for Trials in Clinical Pharmacology ) Trial 04 Study Group.
  • Journal Title: Int J Clin Pharmacol Ther Volume: 52 Issue: 02 Pages: 166-174
  • DOI: 10.5414/cp202001
  • Peer Reviewed
• [Journal Article] QT/QTc study conducted in Japanese adult healthy subjects : a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation (2014)
  • Author(s): Sugiyama A, Hashimoto H, Nakamura Y, Fujita T, Kumagai Y
  • Journal Title: J Clin Pharmacol Volume: 54 Issue: 4 Pages: 446-452
  • DOI: 10.1002/jcph.226
  • Peer Reviewed
• [Journal Article] QT/QTc study conducted in Japanese adult healthy subjects: a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation. (2014)
  • Author(s): Sugiyama A, Hashimoto H, Nakamura Y, Fujita T, Kumagai Y.
  • Journal Title: J Clin Pharmacol Volume: 54 Pages: 446-452
  • Peer Reviewed
• [Journal Article] A common polymorphism in the tissue kallikrein gene is associated with increased urinary excretions of calcium and sodium in Japanese volunteers (2013)
  • Author(s): Fujita T, Yasuda S, Kamata M, Kamata Y, Kumagai Y, Majima M
  • Journal Title: J Hum Genet Volume: 58 Issue: 5 Pages: 758-761
  • DOI: 10.1038/clpt.2011.165
  • NAID: 40019875200
  • Peer Reviewed
• [Journal Article] 適切な薬物治療のための治験データの見方第I相試験実施者の立場から (2013)
  • Author(s): 藤田朋恵
  • Journal Title: アプライド・セラピューティクス Volume: 4 Pages: 29-34
  • Peer Reviewed
• [Journal Article] 健康な日本人における組織カリクレイン遺伝子hKLK1多型解析と表現型に関する検討 (2013)
  • Author(s): 藤田朋恵, 安田修一, 鎌田真理子, 熊谷雄治, 馬嶋正隆
  • Journal Title: 臨床薬理の進歩 Volume: 34 Pages: 131-139
  • Peer Reviewed
• [Journal Article] A common polymorphism in the tissue kallikrein gene is associated with increased urinary excretions of calcium and sodium in Japanese volunteers. (2013)
  • Author(s): Fujita T., Yasuda S., Kamata T., Kamata K., Kumagai Y., Majima M.
  • Journal Title: J Hum Genet. Volume: 58 Issue: 11 Pages: 758-761
  • DOI: 10.1038/jhg.2013.93
  • Peer Reviewed
• [Journal Article] 適切な薬物治療のための治験データの見方 第I相試験実施者の立場から. (2013)
  • Author(s): 藤田朋恵
  • Journal Title: アプライド・セラピューティクス Volume: 4 Pages: 29-34
  • Peer Reviewed
• [Journal Article] 適切な薬物治療のための治験データの見方－第Ｉ相試験実施者の立場から－ (2013)
  • Author(s): 藤田朋恵
  • Journal Title: アプライド・セラピューティクス Volume: 4 Pages: 29-34
• [Journal Article] In vivo kinetics of indoxyl sulfate in humans and its renal interaction with angiotensin-converting enzyme inhibitor quinapril in rats (2011)
  • Author(s): Fujita T, Ishihara K, Yasuda S, Nakamura T, Maeda M, Kobayashi M, Sahashi K, Ikeda Y, Kumagai Y, Majima M
  • Journal Title: J Pharmacol Exp Ther Volume: 341(3) Issue: 3 Pages: 626-33
  • DOI: 10.1124/jpet.111.187732
  • Peer Reviewed
• [Journal Article] Identification of the Rate-Determining Process in the Hepatic Clearance of Atorvastatin in a Clinical Cassette Microdosing Study (2011)
  • Author(s): Maeda K, Ikeda Y, Fujita T, Yoshida K, Azuma Y, Haruyama Y, Yamane N, Kumagai Y, Sugiyama Y
  • Journal Title: Clin Pharmacol Ther Volume: 90 Issue: 2 Pages: 575-581
  • DOI: 10.1038/clpt.2011.108
  • Peer Reviewed
• [Presentation] 健康成人男性の甲状腺機能検査値の変動に関する研究入院拘束が甲状腺機能検査値に及ぼす影響 (2013)
  • Author(s): 中川智枝, 藤田朋恵, 前田実花, 芳田貢, 大原千春, 常田愛子, 佐々木善信, 小泉亮輔, 新井万理子, 天野英樹, 黒山政一, 熊谷雄治
  • Organizer: 第34回日本臨床薬理学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2013-12-06
• [Presentation] 日本人健康成人ボランティアの治験参加動機と認識に関する研究調査票を用いての予備的調査 (2013)
  • Author(s): 小泉亮輔, 前田実花, 脇坂真美, 森亜矢子, 野村今日子, 佐々木善信, 中川智枝, 眞野登喜子, 新井万理子, 藤田朋恵, 黒山政一, 熊谷雄治
  • Organizer: 第34回日本臨床薬理学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2013-12-05
• [Presentation] 新規キサンチンオキシダーゼ阻害剤トピロキソスタットの日本人健康成人におけるQT/QTc評価試験 (2013)
  • Author(s): 中村裕二, 杉山篤, 橋本大哉, 藤田朋恵, 熊谷雄治
  • Organizer: 第34回日本臨床薬理学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2013-12-04
• [Presentation] 健康成人男性の甲状腺機能検査値の変動に関する研究 入院拘束が甲状腺機能検査値に及ぼす影響 (2013)
  • Author(s): 中川 智枝, 藤田 朋恵, 前田 実花, 芳田 貢, 大原 千春, 常田 愛子, 佐々木 善信, 小泉 亮輔, 新井 万理子, 天野 英樹, 黒山 政一, 熊谷 雄治
  • Organizer: 第34回日本臨床薬理学会学術総会
  • Place of Presentation: 東京
• [Presentation] 日本人健康成人ボランティアの治験参加動機と認識に関する研究 調査票を用いての予備的調査 (2013)
  • Author(s): 小泉 亮輔, 前田 実花, 脇坂 真美, 森 亜矢子, 野村 今日子, 佐々木 善信, 中川 智枝, 眞野 登喜子, 新井 万理子, 藤田 朋恵, 黒山 政一, 熊谷 雄治
  • Organizer: 第34回日本臨床薬理学会学術総会
  • Place of Presentation: 東京
• [Presentation] 日本人健康成人でのガバペンチン腎排泄低下に寄与する薬物トランスポーター遺伝子多型検索 (2012)
  • Author(s): 藤田 朋恵,安田 修一, 熊谷 雄治, 馬嶋 正隆
  • Organizer: 第33回日本臨床薬理学会学術総会
  • Place of Presentation: 沖縄
• [Presentation] 日本人での尿中ナトリウム排泄量の個体差要因としてのカリクレイン遺伝子多型検索 (2011)
  • Author(s): 藤田朋恵, 安田修一, 野村今日子, 萩原久美子, 入戸野和代, 高村雅美, 佐橋邦彦, 小林真美, 丸岡奈穂, 中原いちみ, 熊谷雄治, 馬嶋正隆
  • Organizer: 第32回日本臨床薬理学会年会
  • Place of Presentation: 浜松
  • Year and Date: 2011-12-03
• [Remarks] 北里大学医学部薬理学ホームページ
  • URL: http://www.med.kitasato-u.ac.jp/pharm/achievement.html
• [Remarks] 北里大学医学部薬理学
  • URL: http://www.med.kitasato-u.ac.jp/pharm/index.html