In vivo distribution of 14C-labeled N4-behenoyl-1-beta-D-arabinofuranosylcytosine in mice.

In order to clarify the pharmacological characteristics of N4-behenoyl-1-beta-d-arabinofuranosylcytosine (BHAC) and 1-beta-D-arabinofuranosylcytosine (AraC) with regard to their distribution in vivo, 14C-labeled BHAC and 13C-labeled AraC were injected intravenously into mice. Their in vivo distribution was determined by whole-body macroautoradiography and by an oxidation method. The disappearance rates of BHAC[cytosine-2-14C] and BHAC[behenoyl-l-14C] from the blood were slower than that of AraC[cytosine-2-14C], and the elimination rates of BHAC[cytosine-2-14C] and BHAC[behenoyl-14C] into the urine and feces were also slower than that of AraC[cytosine-2-14C]. The total amounts of BHAC[cytosine-2-14C] and BHAC[behenoyl-1-14C] eliminated within 48 hr after the injection were small. AraC[cytosine-2-14C] was equally distributed in each organ, while large amounts of BHAC[cytosine-2-14C] were found in and the placentae. The BHAC[behenoyl-1-14C]level in the thymus was lower than that of BHAC[cytosine-2-14C]. A very low level of radioactivity was found in most of the organs 6 hr after the injection of Arac[cytosine-2-14C], but BHAC[cytosine-2-14C] was observed even 24 hr after the injection. Radioactivity was still found in the liver, spleen, kidneys and adrenal glands of mice injected with BHAC[behenoyl-1-14C] even after 72 hr. In pregnant mice, AraC]cytosine-2-14C] was transmitted to the fetuses, but only a very small amount of 14C-BHAC was transmitted to the fetuses.