Toxicity of liposomal 3'-5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine in mice.
Anticancer Drug Des
; 13(4): 291-305, 1998 Jun.
Article
en En
| MEDLINE
| ID: mdl-9627669
Toxicities of 5-fluoro-2'-deoxyuridine (FUdR) and its liposome incorporated dipalmitoyl derivative (FUdR-dipalmitate) to mouse bone marrow, spleen, liver and ileum were compared after treatment for 6 consecutive days. The applied doses of the two formulations, which were shown earlier to have equal antitumor activity in mouse tumor models, were 600 and 2 mumol/kg respectively. When applied in these doses, toxicity to the hemopoietic system, measured as a decreases in progenitor and precursor cells of the erythroid and granuloid/macrophage lineage in bone marrow and spleen, was more severe for FUdR than for liposomal FUdR-dipalmitate. In the liver, mitotic figures, as indicators of cell division, were absent for both drugs while in control livers the number of cells in mitosis was approximately 2%. Toxicity to the ileum was more severe for liposomal FUdR-dipalmitate than for FUdR and was manifested by granulocyte infiltration, the presence of cell debris, loss of columnar epithelial cells and enlarged nuclei with prominent nucleoli in these cells. Thus, by prolonging the retention time of FUdR in vivo, using liposomes as a vehicle and FUdR-dipalmitate as a lipophilic prodrug, the dose-limiting toxicity appears to shift from bone marrow to the gastrointestinal tract.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Profármacos
/
Floxuridina
/
Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Anticancer Drug Des
Asunto de la revista:
ANTINEOPLASICOS
/
FARMACOLOGIA
Año:
1998
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Estados Unidos