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.