Close correlation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate, an intracellular active metabolite, to the therapeutic efficacy of N(4)-behenoyl-1-beta-D-arabinofuranosylcytosine therapy for acute myelogenous leukemia.

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概要

• 論文の詳細を見る

• N(4)-Behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC), a prodrug of 1-beta-D-arabinofuranosylcytosine, is used effectively for the treatment of leukemia in Japan. BHAC therapy may be more effective if it is delivered in conjunction with monitoring of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP), the intracellular active metabolite of ara-C derived from BHAC. However, previous monitoring methods for ara-CTP were insufficiently sensitive. Here, using our new sensitive method, we evaluated the ara-CTP pharmacokinetics in relation to the therapeutic response in 11 acute myelogenous leukemia patients who received a 2-h infusion of BHAC (70 mg / m(2)) in combination remission induction therapy. ara-CTP could be monitored at levels under 1 mM. BHAC maintained effective levels of plasma ara-C and intracellular ara-CTP for a longer time, even compared with historical values of high-dose ara-C. The area under the concentration-time curve of ara-CTP was significantly greater in the patients with complete remission than in the patients without response. This greater amount of ara-CTP was attributed to the higher ara-CTP concentrations achieved in the responding patients. There was no apparent difference of plasma ara-C pharmacokinetics between the two groups. Thus, for the first time, the ara-CTP pharmacokinetics was evaluated in relation to the therapeutic effect of BHAC, and the importance of ara-CTP was proven. Administration of optimal BHAC therapy may require monitoring of the ara-CTP pharmacokinetics in each individual patient.

• Japanese Cancer Associationの論文
• 2001-09-30

著者

• UEDA Takanori

  First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui

• KISHI Shinji

  First Division, Department of Pathology, Kobe University School of Medicine

• Ueda Takanori

  福井大学 血液腫瘍内科学

• Ueda T

  Department Of Hematology And Oncology University Of Fukui

• Yabe Aya

  Department Of Molecular Biology Institute Of Gerontology Nippon Medical School

• Ueda T

  Department Of Urology Chiba Cancer Center

• Kishi Shinji

  福井大学 医学部第一内科

• Kishi S

  First Department Of Internal Medicine Fukui Medical University

• Ueda Takanori

  First Department Of Internal Medicine Faculty Of Medical Sciences University Of Fukui

• Ueda T

  First Department Of Internal Medicine University Of Fukui

• Kuraishi Yasunobu

  国立金沢病院

• Kuraishi Yasunobu

  Idarubicin Study Group Internal Medicine Iii Jikei University School Of Medicine

• Yamauchi T

  Department Of Hematology And Oncology University Of Fukui

• Yamauchi Takahiro

  福井大学 血液腫瘍内科学

• TSUTANI Hiroshi

  Department of Hematology and Oncology, University of Fukui

• IKEGAYA Satoshi

  Division of Molecular Pathology, University of Fukui, Faculty of Medical Sciences

• YAMAUCHI Takahiro

  First Department of Internal Medicine, University of Fukui

• TSUTANI Hiroshi

  First Department of Internal Medicine, University of Fukui

• YOSHIDA Akira

  First Department of Internal Medicine, Fukui Medical University

• KAWAI Yasukazu

  First Department of Internal Medicine, Fukui Medical University

• IMAMURA Shin

  First Department of Internal Medicine, Fukui Medical University

• FUKUSHIMA Toshihiro

  Internal Medicine, National Kanazawa Hospital

• GOTO Nobuyuki

  Department of Hospital Pharmacy, Fukui Medical University

• URASAKI Yoshimasa

  First Department of Internal Medicine, Fukui Medical University

• FUKUSHIMA Toshihiro

  First Department of Internal Medicine, Fukui Medical University

• IWASAKI Hiromichi

  First Department of Internal Medicine, Fukui Medical University

• MASADA Mikio

  Department of Hospital Pharmacy, Fukui Medical University

• Goto N

  Department Of Hospital Pharmacy Fukui Medical University

• Ueda T

  First Department Of Internal Medicine Fukui Medical School

• Tsutani Hiroshi

  Department Of Hematology And Oncology University Of Fukui

• Goto Nobuyuki

  Department Of Hospital Pharmacy Fukui Medical University

• Yoshida Akira

  First Department Of Internal Medicine University Of Fukui

• Yoshida A

  Department Of Applied Biological Sciences School Of Agricultural Sciences Nagoya University

• Ueda Takahiro

  First Department Of Internal Medicine Fukui Medical University Idarubicin Study Group

• Imamura Shin

  First Department Of Internal Medicine Fukui Medical University

• Kishi Shinji

  First Department Of Internal Medicine University Of Fukui

• Masada Mikio

  Department Of Hospital Pharmacy Fukui Medical University

• Urasaki Yoshimasa

  First Department Of Internal Medicine University Of Fukui

• Kawai Yasukazu

  Department Of Hematology And Oncology University Of Fukui

• Kawai Yasukazu

  First Department Of Internal Medicine Faculty Of Medical Sciences University Of Fukui

• Yoshida A

  First Department Of Internal Medicine University Of Fukui

• Yamauchi Takahiro

  First Department Of Internal Medicine Fukui Medical University

• Iwasaki Hiromichi

  Department Of Hematology And Oncology University Of Fukui

• Fukushima T

  Internal Medicine National Kanazawa Hospital

• Ueda Takeshi

  Department Of Urology Chiba University Graduate School Of Medicine

• Yoshida Akira

  First Department Of Internal Medicine Faculty Of Medical Sciences University Of Fukui

• Goto Nobuyuki

  Department of Drug Informatics, Faculty of Pharmacy, Meijo University

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