Monitoring of intracellular 1-beta-D-arabinofuranosylcytosine 5'-triphosphate in 1-beta-D-arabinofuranosylcytosine therapy at low and conventional doses.

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概要

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• 1-beta-D-Arabinofuranosylcytosine (ara-C) is used empirically at a low, conventional, or high dose. Ara-C therapy may be optimal if it is directed by the clinical pharmacokinetics of the intracellular active metabolite of ara-C, 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP). However, ara-CTP has seldom been monitored during low- and conventional-dose ara-C therapies because detection methods were insufficiently sensitive. Here, with the use of our newly established method (Cancer Res., 56, 1800 -- 1804 (1996)), ara-CTP was monitored in leukemic cells from acute myelogenous leukemia patients receiving low- or conventional-dose ara-C [subcutaneous ara-C administration (10 mg / m(2) ) (3 patients), continuous ara-C infusion (20 or 70 mg / m(2) / 24 h) (7 patients), 2-h ara-C infusion (70 mg / m(2) ) (4 patients), and 2-h infusion of N(4)-behenoyl-1-beta-D-arabinofuranosylcytosine, a deaminase-resistant ara-C derivative (70 mg / m(2) ) (6 patients)]. Ara-CTP could be determined at levels under 1 microM. There was a close correlation between the elimination half-life values of the plasma ara-C and the intracellular ara-CTP. The presence of ara-C in the plasma was important to maintain ara-CTP. The continuous ara-C and the 2-h N(4)-behenoyl-1-beta-D-arabinofuranosylcytosine infusions maintained ara-CTP and the plasma ara-C longer than the subcutaneous ara-C or the 2-h ara-C infusion. They also afforded relatively higher ara-CTP concentrations, and consequently produced ara-CTP more efficiently than the 2-h ara-C infusion. Different administration methods produced different quantities of ara-CTP even at the same dose.

• Japanese Cancer Associationの論文
• 2001-05-31

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

• 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

• 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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