Distribution and metabolism of lipsome-encapsulated and free 1-beta-D-arabinofuranosylcytosine (Ara-C) in dog and mouse tissues.
The effect of liposome encapsulation of the metabolic activation (phosphorylation) and degradation (deamination) of arabinofuranosylcytosine (Ara-C) in liver and spleen of dogs and mice was investigated. Ara-C in free or liposome-encapsulated form was administered i.v. to dogs and DBA2/CR mice bearing leukemia L1210. At various times after injection the concentration of Ara-C and Ara-C metabolites in the blood, liver and spleen was measured. It was shown that liposome encapsulation results in an increased Ara-C/arabinofuranosyluracil ratio in the liver and spleen of dogs and leukemic mice and that encapsulated Ara-C generates a sustained level of Ara-C triphosphate in the liver and spleen of leukemic mice. These results clearly indicate that 1) encapsulated Ara-C is protected against deamination in the liver, 2) encapsulated Ara-C is slowly released from liposomes in liver and spleen and 3) that liposomes may act as a local depot for Ara-C in these tissues.
D000818:Animals; D001646:Bile / Q000378:metabolism; D003561:Cytarabine / Q000008:administration & dosage* / Q000378:metabolism; D003641:Deamination; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage; D008099:Liver / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D008081:Liposomes; D003561:Cytarabine