Pharmacokinetics of N4-octadecyl-1-beta-D-arabinofuranosylcytosine in plasma and whole blood after intravenous and oral administration to mice.

Abstract	N4-octadecyl-1-beta-D-arabinofuranosylcytosine (NOAC) is a new cytotoxic derivative of cytosine arabinoside with improved cytotoxic activity and stability against deamination. Its pharmacokinetics were studied in mice. The drug was administered intravenously and orally to ICR mice to assess its pharmacokinetic parameters in plasma and whole blood. The lipophilic drug was administered in small unilamellar liposomes 100-400 nm in diameter. The concentrations of NOAC in plasma and erythrocytes were determined by high-performance liquid chromatography (HPLC). When given orally a rather low amount of the delivered NOAC was absorbed as the unchanged drug, resulting in a bioavailability of 1.1% from the plasma and 12.9% from whole blood. As shown elsewhere, the amount of drug absorbed is sufficient to provide excellent cytotoxic activity in the L1210 leukemia and in human xenograft models after oral administration. The mean residence time of NOAC after intravenous administration was 3.5 h in plasma and 6 h in whole blood giving NOAC a terminal half-life in blood substantially longer than that of cytosine arabinoside. After oral administration the mean residence time was 18 h in plasma and whole blood. In summary, NOAC has a prolonged half-life after intravenous administration compared with cytosine arabinoside. The distribution of NOAC in blood is highly dependent on its mode of administration.
Authors	K M Rentsch, R A Schwendener, H Schott, E Hänseler
Journal	The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 49 Issue 11 Pg. 1076-81 (Nov 1997) ISSN: 0022-3573 [Print] England
PMID	9401941 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Cytarabine N(4)-oleylcytosine arabinoside
Topics	Administration, Oral Animals Antineoplastic Agents (administration & dosage, blood, pharmacokinetics) Area Under Curve Biological Availability Chromatography, High Pressure Liquid Cytarabine (administration & dosage, analogs & derivatives, blood, pharmacokinetics) Female Injections, Intravenous Intestinal Absorption Metabolic Clearance Rate Mice Mice, Inbred ICR

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