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Order-made pharmacotherapy based on MDR1 genotyping

Research Project

Project/Area Number 15590130
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionKobe University

Principal Investigator

SAKAEDA Toshiyuki  Kobe University, Hospital, Associate Professor, 医学部附属病院, 助教授 (00304098)

Co-Investigator(Kenkyū-buntansha) OKUMURA Katsuhiko  Kobe University, Hospital, Professor, 医学部附属病院, 教授 (60025707)
AOYAMA Nobuo  Kobe University, Hospital, Associate Professor, 医学部附属病院, 助教授 (30243299)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsDrug transporters / MDR1 / Gene / Genotyping / Pharmacogenomics / Pharmacogenetics / Digixin / Cyclosporine / MDRI / ファーマコジュネティクス / ジゴキシン
Research Abstract

This research was conducted to examine the possibility of MDR1 genotyping to establish the order-made pharmacotherapy. MDR1 is a 170kDa membrane protein, which is expressed in the normal tissues including intestine, brain and kidneys, and acts as efflux transporter of exogenous toxic substances out of the cells, and therefore regulates the pharmacokinetics of a number of drugs. Herein, we elucidated that 1)the serum concentration-time profiles of digoxin after single oral administration was defined by MDR1 C3435T, located in exon 26; 2)the expression of MDR1 mRNA in the intestinal mucosa was defined also by MDR1 C3435T. Briefly, the digoxin concentrations were higher in the subjects with C-allele, and the expression of MDR1 mRNA was lower in the subjects. Based on these investigations with healthy subjects, we also found that 3)cyclosporine pharmacokinetics was defined by MDR1 C3435T. These data were published as 6 original articles and 4 review articles.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004 2003 2002 2001 Other

All Journal Article (20 results) Publications (1 results)

  • [Journal Article] Cyclosporine A absorption profiles in children with nephritic syndrome2005

    • Author(s)
      K.Nozu, et al.
    • Journal Title

      Pediatr.Nephrol. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclosporin A absorption profiles in children with nephrotic syndrome2005

    • Author(s)
      K.Nozu, K.Iijima, T.Sakaeda, K.Okumura, K.Nakanishi, N.Yoshikawa, M.Honda, M.Ikeda, M.Matsuo
    • Journal Title

      Pediatr Nephrol.(PMID: 15856324) (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclosporine A absorption profiles in children with nephritic,2005

    • Author(s)
      K.Nozu, et al.
    • Journal Title

      Pediatr.Nephrol. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pharmacogenetics of drug transporters and its impact on the pharmacotherapy2004

    • Author(s)
      T.Sakaeda, T.Nakamura, K.Okumura
    • Journal Title

      Curr Top.Med. Chem.(PMID: 15379652) 4(13)

      Pages: 1385-1398

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pharmacogenetics of MDR and MRP subfamilies2004

    • Author(s)
      N.Okamura, T.Sakaeda, K.Okumura
    • Journal Title

      Personalized Med.(PMID: not defined yet) 1(1)

      Pages: 85-104

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MDR1 genotype-related duodenal absorption rate of digoxin in healthy Japanese subjects2003

    • Author(s)
      Y.Morita, et al.
    • Journal Title

      Pharm.Res.

      Pages: 552-556

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MDR1 genotype-related duodenal absorption rate of digoxin in healthy Japanese subjects2003

    • Author(s)
      Y.Morita, T.Sakaeda, M.Horinouchi, T.Nakamura, K.Kuroda, I.Miki, K.Yoshimura, T.Sakai, D.Shirasaka, N.Aoyama, M.Kasuga, K.Okumura
    • Journal Title

      Pharm.Res.(PMID: 12739761) 20(4)

      Pages: 552-556

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pharmacogenetics of MDR1 and its impact on the pharmacokinetics and pharmacodynamics of drugs2003

    • Author(s)
      T.Sakaeda, T.Nakamura, K.Okumura
    • Journal Title

      Pharmacogenomics(PMID: 12831320) 4(4)

      Pages: 397-410

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of the mutation ( C3435T ) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects2002

    • Author(s)
      T.Nakamura, et al.
    • Journal Title

      Clin.Pharmacol.Ther. 71(4)

      Pages: 297-303

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of polymorphisms of MDR1, MRP1, and MRP2 genes on their mRNA expression levels in duodenal enterocytes of healthy Japanese subjects2002

    • Author(s)
      Y.Moriya, et al.
    • Journal Title

      Biol.Pharm.Bull. 25(10)

      Pages: 1356-1359

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Significant genetic linkage of MDR1 polymorphisms at positions 3435 and 2677: functional relevance to pharmacokinetics of digoxin2002

    • Author(s)
      M.Horinouchi, et al.
    • Journal Title

      Pharm.Res. 19(10)

      Pages: 1581-1585

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects2002

    • Author(s)
      T.Nakamura, T.Sakaeda, M.Horinouchi, T.Tamura, N.Aoyama, T.Shirakawa, M.Matsuo, M.Kasuga, K.Okumura
    • Journal Title

      Clin.Pharmacol.Ther. (PMID: 11956513) 71(4)

      Pages: 297-303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of polymorphisms of MDR1, MRP1, and MRP2 genes on their mRNA expression levels in duodenal enterocytes of healthy Japanese subjects2002

    • Author(s)
      Y.Moriya, T.Nakamura, M.Horinouchi, T.Sakaeda, T.Tamura, N.Aoyama, T.Shirakawa, A.Gotoh, S.Fujimoto, M.Matsuo, M.Kasuga, K.Okumura
    • Journal Title

      Biol.Pharm.Bull(PMID: 12392094) 25(10)

      Pages: 1356-1359

    • NAID

      110003638910

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Significant genetic linkage of MDR1 polymorphisms at positions 3435 and 2677 : functional relevance to pharmacokinetics of digoxin2002

    • Author(s)
      M.Horinouchi, T.Sakaeda, T.Nakamura, Y.Morita, T.Tamura, N.Aoyama, M.Kasuga, K.Okumura
    • Journal Title

      Pharm.Res.(PMID: 12425480) 19(10)

      Pages: 1581-1585

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MDR1 genotype-related pharmacokinetics and pharmacodynamics2002

    • Author(s)
      T.Sakaeda, T.Nakamura, K.Okumura
    • Journal Title

      Biol.Pharm.Bull.(PMID: 12419946) 25(11)

      Pages: 1391-1400

    • NAID

      110003608251

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of the mutation (C3435T) at exon 26 of the MDR1,2002

    • Author(s)
      T.Nakamura, et al.
    • Journal Title

      Clin.Pharmacol.Ther. 71(4)

      Pages: 297-303

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of polymorphisms of MDR1, MRP1, and MRP2 genes,2002

    • Author(s)
      Y.Moriya, et al.
    • Journal Title

      Biol.Pharm.Bull. 25(10)

      Pages: 1356-1359

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Significant genetic linkage of MDR1 polymorphisms at,2002

    • Author(s)
      M.Horinouchi, et al.
    • Journal Title

      Pharm.Res. 19(10)

      Pages: 1581-1585

    • Related Report
      2004 Annual Research Report
  • [Journal Article] MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects2001

    • Author(s)
      T.Sakaeda, et al.
    • Journal Title

      Pharm.Res. 18(10)

      Pages: 1400-1404

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects2001

    • Author(s)
      T.Sakaeda, T.Nakamura, M.Horinouchi, M.Kakumoto, N.Ohmoto, T.Sakai, Y.Morita, T.Tamura, N.Aoyama, M.Hirai, M.Kasuga, K.Okumura
    • Journal Title

      Pharm.Res.(PMID: 11697464) 18(10)

      Pages: 1400-1404

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Y.Morita et al.: "MDRI Gemotype-related Duodenal Absorption Rete of Digoxin in Japanese Subjects"Pharm.Res.. 20(4). 552-556 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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