Comparison of lymphatic uptake, metabolism, excretion, and biodistribution of free and liposome-entrapped (/sup 14/C)cytosine beta-D-arabinofuranoside following intraperitoneal administration to rats
Free (/sup 14/C)cytosine beta-D-arabinofuranoside ((/sup 14/C)ara-C) was completely absorbed from the peritoneal cavity of thoracic duct-cannulated rats by 6 hr after ip dosing. /sup 14/C 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 /sup 14/C-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.
- Research Organization:
- Laboratory of Chemical Pharmacology, National Cancer Institute, NIH, Bethesda, MD
- OSTI ID:
- 6709612
- Journal Information:
- Drug Metab. Dispos.; (United States), Vol. 10:1
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
CARBON 14 COMPOUNDS
ISOTOPE APPLICATIONS
CYTOSINE
METABOLISM
TISSUE DISTRIBUTION
BIOLOGICAL PATHWAYS
INTRAPERITONEAL INJECTION
LYMPH
METASTASES
NEOPLASMS
PATHOLOGY
PERITONEUM
RATS
URINE
AMINES
ANIMALS
AZINES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
DISEASES
DISTRIBUTION
HETEROCYCLIC COMPOUNDS
INJECTION
INTAKE
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MEMBRANES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PYRIMIDINES
RODENTS
SEROUS MEMBRANES
VERTEBRATES
WASTES
550604* - Medicine- Unsealed Radionuclides in Therapy- (1980-)
550201 - Biochemistry- Tracer Techniques
550901 - Pathology- Tracer Techniques