COMPARISON OF LYMPHATIC UPTAKE, METABOLISM, EXCRETION, AND BIODISTRIBUTION OF FREE AND LIPOSOME-ENTRAPPED [C-14]LABELED CYTOSINE BETA-D-ARABINOFURANOSIDE FOLLOWING INTRAPERITONEAL ADMINISTRATION TO RATS

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 10  (1) , 40-46
Abstract
Free [14C]cytosine .beta.-D-arabinofuranoside ([14C]ara-C) was completely absorbed from the peritoneal cavity of thoracic duct-cannulated rats by 6 h after i.p. dosing. 14C levels in most tissues were higher at 4 h than at 12 h after dosing and were generally undetectable at 24 h. By 6 h after treatment only 2% of the dose was recovered in lymph, 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 > 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 given liposome-entrapped ara-C, with 300-1000-fold higher levels present at 4, 12 and 24 h 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 .apprx. 3-fold following liposome entrapment of the drug. The enhanced lymphatic uptake and the localization and persistance of ara-C in lymph nodes resulting from liposome entrapment of the drug may be of benefit in treating tumors in patients that metastasize via lymphatic pathways.