Antitumor activity and pharmacology of 1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate: an orally active derivative of 1-beta-D-arabinofuranosylcytosine.

Abstract	The antitumor activity of 1-beta-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 1-beta-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-beta-D-arabinofuranosylcytosine (ara-C) remained in the range of 0.4 to 0.75 nmol/ml [corrected] for 24 h after oral administration of 100 mg/kg (170 mumol/kg) of C18PCA. These results indicate that C18PCA administered per orally is absorbed intact through the gastrointestinal tract and area-C is released of long period of time. C18PCA is regarded as an orally active depot form of ara-C.
Authors	K Kodama, M Morozumi, K Saitoh, A Kuninaka, H Yoshino, M Saneyoshi
Journal	Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 80 Issue 7 Pg. 679-85 (Jul 1989) ISSN: 0910-5050 [Print] Japan
PMID	2507491 (Publication Type: Journal Article)
Chemical References	Antineoplastic Agents Arabinonucleotides Cytosine Nucleotides Cytarabine 1-arabinofuranosylcytosine-5'-stearylphosphate Cytidine Monophosphate
Topics	Administration, Oral Animals Antineoplastic Agents (administration & dosage, pharmacokinetics) Arabinonucleotides (pharmacokinetics, therapeutic use) Cytarabine (pharmacokinetics, therapeutic use) Cytidine Monophosphate (pharmacokinetics, therapeutic use) Cytosine Nucleotides (therapeutic use) Drug Administration Schedule Leukemia L1210 (drug therapy) Metabolic Clearance Rate Mice Solubility Structure-Activity Relationship

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