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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2001 May;92(5):546–553. doi: 10.1111/j.1349-7006.2001.tb01128.x

Monitoring of Intracellular l‐βD‐Arabinofuranosylcytosine 5′‐Triphosphate in 1‐β‐D‐Arabinofuranosylcytosine Therapy at Low and Conventional Doses

Takahiro Yamauchi 1,✉, Yasukazu Kawai 1, Shinji Kishi 1, Nobuyuki Goto 2, Yoshimasa Urasaki 1, Shin Imamura 1, Toshihiro Fukushima 1, Akira Yoshida 1, Hiromichi Iwasaki 1, Hiroshi Tsutani 1, Mikio Masada 2, Takanori Ueda 1
PMCID: PMC5926735  PMID: 11376564

Abstract

1‐β‐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‐β‐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 myelog‐enous leukemia patients receiving low‐ or conventional‐dose ara‐C [subcutaneous ara‐C administration (10 mg/m2) (3 patients), continuous ara‐C infusion (20 or 70 mg/m2/24 h) (7 patients), 2‐h ara‐C infusion (70 mg/m2) (4 patients), and 2‐h infusion of N4‐behenoyl‐l‐β‐D‐arabinofuranosylcy‐tosine, a deaminase‐resistant ara‐C derivative (70 mg/m2) (6 patients)]. Ara‐CTP could be determined at levels under 1μM. 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 N4‐behenoyl‐l‐β‐D‐arabinofura‐nosylcytosine 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.

Keywords: Ara‐C, Ara‐CTP, Clinical pharmacokinetics, Low and conventional dose

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