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Assessment of conception periods for patients treated with nucleoside analogues based on their intracellular accumulation in erythrocytes.

Research Project

Project/Area Number 20590534
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionUniversity of Tsukuba

Principal Investigator

HOMMA Masato  University of Tsukuba, 大学院・人間総合科学研究科, 准教授 (90199589)

Co-Investigator(Kenkyū-buntansha) KOHDA Yukinao  筑波大学, 大学院・人間総合科学研究科, 教授 (40143482)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords核酸誘導体 / 赤血球内蓄積 / C型慢性肝炎 / リバビリン / 催奇形成 / 避妊期間 / 赤血球内濃度 / SLC29A1 / ゲムシタビン / ジピリダモール / 核酸トランスポーター
Research Abstract

Ribavirin (RBV), a nucleoside analogue, for hepatitis C virus (HCV) eradication requires the patients to have contraception for 6 months after stopping the therapy because of possible deformity caused by RBV. This period is enough to remove plasma RBV with the half-life (T1/2) of 12 days. Intracellular RBV, which is accumulated as the phosphorylated RBV in the tissue including erythrocytes, may require much time to be removed. Plasma and whole blood concentration of RBV were monitored before and after stopping the interferon (IFN)/RBV therapy in 45 HCV patients. Mean plasma and whole blood RBV were 10.1±4.6 and 307.9±146.5 μM, respectively, when IFN/RBV therapy was stopped. The T1/2 for plasma and whole blood RBV were 12.9±4.4 and 23.9±7.5 days, respectively. It was estimated that 79 (51-121) and 176 (130-331) days were required for removing RBV from plasma and whole blood, respectively. Population pharmacokinetic analysis for whole blood RBV revealed that 6 months was not enough for removing RBV from blood in 33% of HCV patients. Six months may not be enough as the contraception period after stopping RBV in patients with longer T1/2 of whole blood RBV.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (9 results)

All 2010 2009 2008

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (6 results)

  • [Journal Article] Morphological transformation and phosphatidylserine exposure in erythrocytes treated with ribavirin2009

    • Author(s)
      Homma M, Hosono H, Hasegawa Y, Kohda Y
    • Journal Title

      Biol Pharm Bull. 32(11)

      Pages: 1940-2

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Morphological Transformation and Phosphatidylserine Exposure in Erythrocytes Treated with Ribavirin2009

    • Author(s)
      Homma M, Hosono H, Hasegawa Y, Kohda Y.
    • Journal Title

      Biol.Pharm.Bull. 32

      Pages: 1940-1942

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blood ribavirin concentration in high-dose ribavirin for adenovirusinduced haemorrhagic cystitis-a case report2008

    • Author(s)
      Homma M, Inoue Y, Hasegawa Y, Kojima H, Kohda Y
    • Journal Title

      J Clin Pharm Ther. 33(1)

      Pages: 75-78

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] ヒト末梢血単核細胞を用いたヌクレオシドトランスポーターの活性評価2010

    • Author(s)
      大木桜子,本間真人,鈴木嘉治,小田竜也,大河内信弘,幸田幸直
    • Organizer
      医療薬学フォーラム2010/第18回クリニカルファーマシーシンポジウム
    • Place of Presentation
      広島
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 末梢血リンパ球SLC29A1 mRNA発現にSLC29A1遺伝子多型が与える影響2009

    • Author(s)
      鈴木嘉治,本間真人,幸田幸直
    • Organizer
      第19回日本医療薬学会年会
    • Place of Presentation
      長崎
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] SLC29A1遺伝子多型が末梢血リンパ球SLC29A1 mRNA発現に及ぼす影響2008

    • Author(s)
      鈴木嘉治,本間真人,幸田幸直
    • Organizer
      第15回日本臓器保存生物医学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Pharmacokinetics of Whole Blood Ribavirin for Estimating Contraception Period after Stopping Interferon and Ribavirin Combination Therapy2008

    • Author(s)
      Homma M, Shiina N, Doki K, Abei M, Matsuzaki Y, Hyodo I, Kohda Y
    • Organizer
      The IXth World Conference on Clinical Pharmacology and Therapeutics
    • Place of Presentation
      (Quebec)カナダ
    • Related Report
      2010 Final Research Report
  • [Presentation] Pharmacokinetics of Whole Blood Ribavirin for Estimating Contraception Period after Stopping Interferon and Ribavirin Combination Therapy2008

    • Author(s)
      M. Homma, N. Shiina, K. Doki, M. Abei, Y. Matsuzaki, I. Hyodo, Y. Kohda
    • Organizer
      The IXth World Conference on Clinical Pharmacology and Therapeutics
    • Place of Presentation
      Quebec City, Canada
    • Related Report
      2008 Annual Research Report
  • [Presentation] SLC29A1遺伝子多型が末梢血リンパ球SLC29A1 mRNA発現に及ぼす影響2008

    • Author(s)
      鈴木嘉治, 本間真人, 幸田幸直
    • Organizer
      第35回日本臓器保存生物医学会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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