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Development of dosing schedule based on molecular clock mechanisms

Research Project

Project/Area Number 18390050
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

OHDO Shigehiro  Kyushu University, Faculty of Pharmaceutical Sciences, Professor (00223884)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥15,880,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2007: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2006: ¥11,200,000 (Direct Cost: ¥11,200,000)
KeywordsBiological rhythm / Biological clock / Clock gene / Chronopharmacology / Chronotherapy
Research Abstract

Mammalians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN). Clock genes are the genes that control the circadian rhythms in physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-hr rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. However, many drugs are still given without regard to the time of day. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. To monitor the rhythmic marker was useful to choose the most appropriate time of day for administration of drugs that increase their therapeutic effects and/or reduce their side effects. On the other hand, several drugs can cause alterations to the 24-hr rhythms, which leads to illness and altered homeostatic regulation. We showed the disruptive effect of interferon on the rhythm of locomotor activity, body temperature and clock genes mRNA expression in the periphery and SCN. The alteration of the clock function, a new concept of adverse effects, was overcome by devising a dosing schedule that minimizes adverse drug effects on clock function. Furthermore, to produce new rhythmicity by manipulating the conditions of living organs by using rhythmic administration of altered feeding schedules or several drugs appears to lead to the new concept of chronopharmacotherapy. One approach to increasing the efficiency of pharmacotherapy is administering drugs at times during which they are best tolerated. Finally, we developed the vector showing rhythmic gene expression for the intelligent chrono-drug delivery system.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (17 results)

All 2008 2007 2006

All Journal Article (15 results) (of which Peer Reviewed: 8 results) Presentation (2 results)

  • [Journal Article] Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian clock genes: A possible mechanism of chemotherapy-induced circadian rhythm disturbances2008

    • Author(s)
      Terazono H, et. al.
    • Journal Title

      Biochemical Pharmacology 75(8)

      Pages: 1616-1622

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The molecular mechanism regulating 24-hr rhythm of CYP2E1 expression in the mouse liver2008

    • Author(s)
      Matsunaga N, et. al.
    • Journal Title

      Hepatology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian clock genes : A possible mechanism of chemotherapy-induced circadian rhythm disturbances2008

    • Author(s)
      Terazono, H., Hamdan, A., Matsunaga, N., Hayasaka, N., Kaji, H., Egawa, T., Makino, K., Shigeyoshi, Y., Koyanagi, S., Ohdo, S
    • Journal Title

      Biochemical Pharmacology 75(8)

      Pages: 1616-1622

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The molecular mechanism regulating 24-hr rhythm of CYP2E1 expression in the mouse liver (in press)2008

    • Author(s)
      Matsunaga, N., Ikeda, M., Takiguchi, T., Koyanagi, S., Ohdo, S.
    • Journal Title

      Hepatology

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian clock genes: A possible mechanism of chemotherapy-induced circadian rhythm disturbances.2008

    • Author(s)
      Terazono H, et. al.
    • Journal Title

      Biochem Pharmacol 75(8)

      Pages: 1616-1622

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The molecular mechanism regulating 24-hr rhythm of CYP2E1 expression in the mouse liver.2008

    • Author(s)
      Matsunaga N, et. al.
    • Journal Title

      Hepatology (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular basis for rhythmic expression of CYP3A4 in serum-shocked HepG2 cells2007

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

      Pharmacogenetics and Genomics 17(12)

      Pages: 1047-1056

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Molecular basis for rhythmic expression of CYP3A4 in serum-shocked HepG2 cells2007

    • Author(s)
      Takiguchi, T., Tomita, M., Matsunaga, N., Nakagawa, H., Koyanagi, S., Ohdo, S
    • Journal Title

      Pharmacogenetics and Genomics 17(12)

      Pages: 1047-1056

    • NAID

      130005024316

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Molecular basis for rhythmic expression of CYP3A4 in serum-shocked HepG2 cells.2007

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

      Pharmacogenetics and Genomics 17(12)

      Pages: 1047-1056

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucocorticoid regulation of 24-hour oscillation in interferon receptor gene expression in mouse liver2006

    • Author(s)
      Koyanagi S, et. al.
    • Journal Title

      Endocrinology 147(11)

      Pages: 5034-5040

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Basis for dosing time-dependent change in the anti-tumor effect of imatinib in mice2006

    • Author(s)
      Nakagawa H, et. al.
    • Journal Title

      Biochemical Pharmacology 72(10)

      Pages: 1237-1245

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Glucocorticoid regulation of 24-hour oscillation in interferon receptor gene expression in mouse liver2006

    • Author(s)
      Koyanagi, S., Suyama, H., Kuramoto, Y., Matsunaga, N., Takane, H., Soeda, S., Shimeno, H., Higuchi, S., Ohdo, S
    • Journal Title

      Endocrinology 147(11)

      Pages: 5034-5040

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Basis for dosing time-dependent change in the anti-tumor effect of imatinib in mice2006

    • Author(s)
      Nakagawa, H., Takiguchi, T., Nakamura, M., Furuyama, A., Koyanagi, S., Aramaki, H., Higuchi, S., Ohdo, S
    • Journal Title

      Biochemical Pharmacology 72(10)

      Pages: 1237-1245

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Glucocorticoid regulation of 24-hour oscillation in interferon receptor gene expression in mouse liver2006

    • Author(s)
      Koyanagi S, et al.
    • Journal Title

      Endocrinology 147・11

      Pages: 5034-5040

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Basis for dosing time-dependent change in the anti-tumor effect of imatinib in mice2006

    • Author(s)
      Nakagawa H, et al.
    • Journal Title

      Biochemical Pharmacology 72

      Pages: 1237-1245

    • Related Report
      2006 Annual Research Report
  • [Presentation] Chronopharmacology of antitumor drugs in mice2007

    • Author(s)
      Ohdo, S
    • Organizer
      The 3rd Asian Symposium for Pharmaceutical Sciences
    • Place of Presentation
      Japan(Sasebo)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Plenary lecture, Chronopharmacology of antitumor drugs : molecular clock mechanisms2007

    • Author(s)
      Ohdo, S
    • Organizer
      2nd World Congress of Chronobiology
    • Place of Presentation
      Japan(Tokyo)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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