%0 Journal Article %A Sibylle K. M. Koller-Lucae %A Herbert Schott %A Reto A. Schwendener %T Interactions with Human Blood in Vitro and Pharmacokinetic Properties in Mice of Liposomal N4-Octadecyl-1-β-d-arabinofuranosylcytosine, A New Anticancer Drug %D 1997 %J Journal of Pharmacology and Experimental Therapeutics %P 1572-1580 %V 282 %N 3 %X The interactions of N4-octadecyl-1-β-d-arabinofuranosylcytosine (NOAC), a lipophilic derivative of 1-β-d-arabinofuranosylcytosine (ara-C), were studiedin vitro with human blood components. Binding of NOAC incorporated into liposomes to erythrocytes (Ec) was saturated at 63 nmol/109 Ec and binding analysis resulted in a weak affinity of 3 × 103 liters/mol and 4 × 107 binding sites per Ec. The Ec partition coefficientD Ec was approximately 4, which demonstrates the high accumulation of NOAC in Ec membranes. The calculated fractionf b of drug bound to plasma proteins was 30%. Analysis of serum protein binding of NOAC was done by density gradient ultracentrifugation and agarose gel electrophoresis. Liposomal NOAC was distributed to low-density lipoproteins (LDL) at 36%, to high-density lipoproteins at 21%, to albumin and other proteins at 12% and to very-low-density lipoproteins at 5%. Comparable results were obtained for the analog N4-hexadecyl-1-β-d-arabinofuranosylcytosine and when the drugs were dissolved in dimethyl sulfoxide. The biodistribution of liposomal NOAC in ICR mice after intravenous application revealed a biphasic blood concentration versustime curve with a distribution half-life t 1/2αof 23 min and an elimination half-life t 1/2βof 7 h. The drug was distributed mainly into the liver with an organ load of 69% and with an elimination half-life of 8 h. The strong affinity of NOAC to LDL might be exploited for the enhanced uptake of the drug in tumor cells expressing high numbers of LDL receptor molecules. The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/282/3/1572.full.pdf