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.

• Material Type: 文書・図像類
• Title: 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.
• Author/Editor: Yamauchi, Takahiro; Kawai, Yasukazu; Goto, Nobuyuki; Kishi, Shinji; Imamura, Shin; Yoshida, Akira; Urasaki, Yoshimasa; Fukushima, Toshihiro; Iwasaki, Hiromichi; Tsutani, Hiroshi; Masada, Mikio; Ueda, Takanori
• Author Heading: Yamauchi, Takahiro; Kawai, Yasukazu; Goto, Nobuyuki; Kishi, Shinji; Imamura, Shin; Yoshida, Akira; Urasaki, Yoshimasa; Fukushima, Toshihiro; Iwasaki, Hiromichi; Tsutani, Hiroshi; Masada, Mikio; Ueda, Takanori
• Publication, Distribution, etc.: Japanese Cancer Association
• Publication Date: 2001-09
• Publication Date (W3CDTF): 2001-09
• Periodical title: Japanese journal of cancer research : Gann
• No. or year of volume/issue: 92 9
• Volume: 92
• Issue: 9
• Pages: 975-982
• Text Language Code: eng
• Subject Heading: BHAC; ara-C; ara-CTP; Clinical pharmacokinetics; AUC
• Target Audience: 一般
• Note (General): 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.
• Access Restrictions: 限定公開
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 福井大学 : 福井大学学術機関リポジトリ