The mechanisms of the variability in the intestinal absorption of nucleoside drugs

• Project/Area Number: 23790176
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: University of Toyama
• Principal Investigator: ISHIDA Kazuya 富山大学, 大学院医学薬学研究部(薬学), 助教 (90550509)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 薬物動態 / トランスポーター / 臨床試験

Research Abstract

The findings in the present study indicate that the variable bioavailability (F) of mizoribine is one of the factors for the interindividual pharmacokinetic variability of the drug in healthy volunteers and adult and pediatric recipients of renal transplantation, and that the genetic polymorphism of concentrative nucleoside transporter (CNT) 1 is partly involved in the variable F of mizoribine. In addition, the membrane transport of mizoribine in intestinal epithelial cells is mediated by CNT1, CNT2, equilibrative nucleoside transporters (ENTs), and unidentified efflux transporter(s).

Research Products

• [Journal Article] Effect of Salt Intake on Bioavailability of Mizoribine in Healthy Japanese Males (2013)
  • Author(s): Ishida K, Fukao M, Watanabe H, Taguchi M, Miyawaki T, Matsukura H, Uemura O, Zhang Z, Unadkat JD, Hashimoto Y
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 28 Issue: 1 Pages: 75-80
  • DOI: 10.2133/dmpk.DMPK-12-NT-043
  • NAID: 130004463290
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed
• [Journal Article] Variability of Bioavailability and Intestinal Absorption Characteristics of Bisoprolol (2013)
  • Author(s): Kazuya Ishida
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 28 Issue: 6 Pages: 491-496
  • DOI: 10.2133/dmpk.DMPK-13-RG-017
  • NAID: 130004463332
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed
• [Journal Article] Population pharmacokinetics of mizoribine in pediatric recipients of renal transplantation (2012)
  • Author(s): Ishida, Kazuya
  • Journal Title: Clin.Exp.Nephrol. Volume: (In press) Issue: 5 Pages: 799-804
  • DOI: 10.1007/s10157-012-0616-4
  • NAID: 10031122270
  • Peer Reviewed
• [Journal Article] Population pharmacokinetics of mizoribine in adult recipients of renal transplantation (2011)
  • Author(s): Ishida, Kazuya
  • Journal Title: Clin.Exp.Nephrol. Volume: 15 Issue: 6 Pages: 900-906
  • DOI: 10.1007/s10157-011-0487-0
  • NAID: 10030341853
  • Peer Reviewed
• [Journal Article] Effect of Genetic Polymorphisms of SLC28A1, ABCG2, and ABCC4 on Bioavailability of Mizoribine in Healthy Japanese Males (2011)
  • Author(s): Fukao, Miki
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 26 Issue: 5 Pages: 538-543
  • DOI: 10.2133/dmpk.DMPK-11-NT-040
  • NAID: 130004463218
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed
• [Presentation] Variability of bioavailability and intestinal absorption characteristics of bisoprolol (2013)
  • Author(s): Ishida K, Horie A, Nishimura M, Taguchi M, Fujii N, Nozawa T, Inoue H, Hashimoto Y
  • Organizer: 第7回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 仙台
• [Presentation] Variability of bioavailability of mizoribine in healthy males and mechanisms of barrier function for intestinal absorption (2013)
  • Author(s): Ishida K, Fukao M, Takabayashi M, Taguchi M, Itoh H, Hashimoto Y
  • Organizer: 日本薬物動態学会第28回年会
  • Place of Presentation: 東京
• [Presentation] Variability of bioavailability of mizoribine in healthy males and mechanisms of barrier function for intestinal absorption. (2013)
  • Author(s): Kazuya Ishida
  • Organizer: 日本薬物動態学会第28回年会
  • Place of Presentation: タワーホール船堀（東京都）
• [Presentation] Variability of bioavailability and intestinal absorption characteristics of bisoprolol (2013)
  • Author(s): Kazuya Ishida
  • Organizer: 第7回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 東北大学片平キャンパス さくらホール（宮城県）
• [Presentation] Zhang Z, Unadkat JD,橋本征也,ミゾリビンの吸収に及ぼすナトリウムの影響 (2012)
  • Author(s): 渡邉ひとみ,石田和也,深尾美紀,田口雅登,宮脇利男,松倉裕喜,上村治
  • Organizer: 日本薬学会北陸支部第124回例会
  • Place of Presentation: 富山
  • Year and Date: 2012-11-18
• [Presentation] Improvement of the intestinal absorption of mizoribine by salt intake in healthy Japanese males (2012)
  • Author(s): Fukao M, Ishida K, Watanabe H, Taguchi M, Miyawaki T, Matsukura H, Uemura O, Zhang Z, Unadkat JD, Hashimoto Y
  • Organizer: 日本薬物動態学会第27回年会
  • Place of Presentation: 東京
• [Presentation] Effect of salt intake on bioavailability of mizoribine in healthy Japanese males (2012)
  • Author(s): Ishida K, Fukao M, Watanabe H, Taguchi M, Miyawaki T, Matsukura H, Uemura O, Zhang Z, Unadkat JD, Hashimoto Y
  • Organizer: 18^<th> North American ISSX meeting
  • Place of Presentation: Dallas
• [Presentation] Effect of salt intake on bioavailability of mizoribine in healthy Japanese males (2012)
  • Author(s): Kazuya Ishida
  • Organizer: 18th North American ISSX meeting
  • Place of Presentation: Hilton Anatole Dallas Hotel, Dallas, Texas, USA
• [Presentation] Improvement of the intestinal absorption of mizoribine by salt intake in healthy Japanese males (2012)
  • Author(s): Miki Fukao
  • Organizer: 日本薬物動態学会第27回年会
  • Place of Presentation: タワーホール舟堀（東京都）
• [Presentation] 培養ヒト腸上皮細胞を用いたミゾリビンの消化管吸収機構解析 (2011)
  • Author(s): 横田篤,森川真圭,石田和也,田口雅登,橋本征也
  • Organizer: 日本薬学会北陸支部第123回例会
  • Place of Presentation: 金沢
  • Year and Date: 2011-11-27
• [Presentation] 健常成人のミゾリビンの消化管吸収に対する遺伝と食塩摂取の影響 (2011)
  • Author(s): 深尾美紀,渡邉ひとみ,石田和也,田口雅登,橋本征也,松倉裕喜,宮脇利男
  • Organizer: 日本薬学会北陸支部第123回例会
  • Place of Presentation: 金沢
  • Year and Date: 2011-11-27
• [Presentation] Effect of Genetic Polymorphisms of SLC28A1, ABCG2, and ABCC4 on Bioavailability of Mizoribine in Healthy Japanese Males (2011)
  • Author(s): Ishida K, Fukao M, Watanabe H, Taguchi M, Matsukura H, Miyawaki T, and Hashimoto Y
  • Organizer: 2011 American Association of Pharmaceutical Scientists Annual Meeting
  • Place of Presentation: Washington, D.C.
• [Presentation] Effect of genetic polymorphisms of nucleoside and efflux transporters on bioavailability of mizoribine (2011)
  • Author(s): Fukao M, Ishida K, Taguchi M, Matsukura H, Miyawaki T, and Hashimoto Y
  • Organizer: 日本薬物動態学会第26年会
  • Place of Presentation: 広島
• [Presentation] Effect of genetic polymorphisms of SLC28A1, ABCG2, and ABCC4 on bioavailability of mizoribine in healthy Japanese males (2011)
  • Author(s): Kazuya Ishida
  • Organizer: 2011 AAPS Annual Meeting and Exposition
  • Place of Presentation: Walter E. Washington Convention Center, Washington, DC, USA
• [Presentation] Effect of genetic polymorphisms of nucleoside and efflux transporters on bioavailability of mizoribine in healthy Japanese males (2011)
  • Author(s): Miki Fukao
  • Organizer: 日本薬物動態学会第26回年会
  • Place of Presentation: 広島国際会議場(広島県）
• [Remarks]
  • URL: http://www.pha.u-toyama.ac.jp/anzensei/index-j.html