Comparison of lymphatic uptake, metabolism, excretion, and biodistribution of free and liposome-entrapped [14C]cytosine beta-D-arabinofuranoside following intraperitoneal administration to rats.
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.
D000042:Absorption; D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D003561:Cytarabine / Q000378:metabolism*; D008081:Liposomes / Q000008:administration & dosage*; D008196:Lymph / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008208:Lymphatic System / Q000378:metabolism; D008297:Male; D010529:Peritoneal Cavity / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D008081:Liposomes; D003561:Cytarabine