Open AccessAntitumor Activity and Pharmacology of 1‐β‐D‐Arabinofuranosylcytosine‐5′‐stearylphosphate: An Orally Active Derivative of 1‐β‐D‐Arabinofuranosylcytosine
Author(s) -
Kodama Kenjiro,
Morozumi Manami,
Saitoh Kenichi,
Kuninaka Akira,
Yoshino Hiroshi,
Saneyoshi Mineo
Publication year - 1989
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1989.tb01696.x
Subject(s) - pharmacology , oral administration , chemistry , prodrug , orally active , cytarabine , gastrointestinal tract , pharmacokinetics , leukemia , medicine , biochemistry
The antitumor activity of l‐β‐D‐arabinofuranosylcytosine‐5′‐alkylphosphates (CnPCAs) against L1210 leukemia in mice after oral administration was demonstrated. The optimum length of the alkyl group on the phosphate moiety of CnPCA for exhibiting a high antitumor activity was found to be between tetradecyl (C14) and tricosyl (C23). The most active alkyl derivative in this system was found to be l‐β‐D‐arabinofuranosylcytosine‐5′‐stearylphosphate (C18PCA). The optimum and minimum effective doses of C18PCA were 100 and 6,25 mg/kg/day (q1d, day 1 to day 5), respectively. The maximum T/C% of C18PCA was approximately 220. The antitumor activity of C18PCA was not greatly dependent on the treatment schedule and route. Plasma concentration of 1‐β‐D‐arabinofurano‐sylcytosine (ara‐C) remained in the range of 0.4 to 0.75 μmol/ml for 24 h after oral administration of 100 mgAg (170 μmol/kg) of C18PCA. These results indicate that C18PCA administered per orally is absorbed intact through the gastrointestinal tract and ara‐C is released for a long period of time. C18PCA is regarded as an orally active depot form of ara‐C