Parker R J, Priester E R, Sieber S M
Drug Metab Dispos. 1982 Jan-Feb;10(1):40-6.
Free [14C]cytosine beta-D-arabinofuranoside ([14C]ara-C) was completely absorbed from the peritoneal cavity of thoracic duct-cannulated rats by 6 hr after ip dosing. 14C levels in most tissues were higher at 4 hr than at 12 hr after dosing and were generally undetectable at 24 hr. By 6 hr after treatment only 2% of the dose was recovered in lymph, whereas 90% had been excreted in urine. Liposome entrapment of ara-C reduced the rates at which the drug was absorbed from the peritoneal cavity and excreted in urine while enhancing lymphatic uptake of the drug by more than 10-fold. Radioactivity in plasma and most tissues achieved higher concentrations and persisted for longer periods in rats given liposome-entrapped ara-C than in rats receiving the free drug. Most striking was the localization of 14C-activity in renal and thoracic lymph nodes of rats give liposome-entrapped ara-C, with 300 to 1000-fold higher levels present at 4, 12, and 24 hr after dosing than in corresponding lymph nodes of rats receiving the free drug. The metabolic conversion of ara-C to uracil beta-D-arabinofuranoside (ara-U) was reduced by approximately 3-fold following liposome entrapment of the drug. The enhanced lymphatic uptake and the localization and persistence of ara-C in lymph nodes resulting from liposome entrapment of the drug may be of benefit in treating tumors that metastasize via lymphatic pathways.
游离的[14C]胞嘧啶β-D-阿拉伯呋喃糖苷（[14C]阿糖胞苷）腹腔注射给药后6小时，在胸导管插管大鼠的腹腔内被完全吸收。给药后4小时，大多数组织中的14C水平高于12小时，24小时时通常检测不到。治疗后6小时，只有2%的剂量在淋巴液中回收，而90%已随尿液排出。阿糖胞苷的脂质体包封降低了药物从腹腔吸收和经尿液排泄的速率，同时使药物的淋巴摄取增加了10倍以上。与接受游离药物的大鼠相比，给予脂质体包封阿糖胞苷的大鼠血浆和大多数组织中的放射性达到更高浓度并持续更长时间。最显著的是，给予脂质体包封阿糖胞苷的大鼠肾脏和胸段淋巴结中有14C活性的定位，给药后4、12和24小时其水平比接受游离药物的大鼠相应淋巴结中的水平高300至1000倍。药物脂质体包封后，阿糖胞苷向尿嘧啶β-D-阿拉伯呋喃糖苷（阿糖尿苷）的代谢转化降低了约3倍。药物脂质体包封导致阿糖胞苷在淋巴结中的淋巴摄取增强、定位和持续存在，这可能有利于治疗通过淋巴途径转移的肿瘤。
