Improvement in 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) concentration by 5-fluorouracil-polyethylene-glycol-liposomes in abdominal stop-flow: treatment of VX2 liver-tumor-bearing rabbits.
The application of liposome-encapsulated cytostatics results in higher concentrations in tumor tissue. This effect can be further increased by blood flow retardation with longer retention time in the tumor and by arterial administration. In abdominal stop-flow therapy, a separate partial circulation with a defined flow is realized via a roller pump under hypoxic conditions. Forty chinchilla rabbits with VX-2 liver tumors were treated either intra-aortally (stop-flow therapy) or systemically with 50 mg 5-FU or 5-FU-PEG liposomes. During therapy, pH and pO2 were measured at regular intervals. After 20 minutes, concentrations of 5-FU and its metabolite FdUrd were determined by HPLC in different organs and the liver tumor. Compared to the i.v. application of monosubstances, the combination of i.a. 5-FU-PEG liposomes and flow retardation increased the concentration in tumor tissue by a factor of 44 and even 100-fold in the para-aortal lymph nodes (LN). The concentration of 5-FU and FdUrd was increased by flow reduction, intraaortal application and liposomal encapsulation of 5-FU.
Pohlen
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U
Department of Surgery, Charité - Universitaetsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. SU1110@aol.com
Rieger
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H
Binnenhei
M
M
Reszka
R C
RC
Buhr
H J
HJ
Berger
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G
D000818:Animals; D001682:Biological Availability; D001783:Blood Flow Velocity; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005467:Floxuridine / Q000493:pharmacokinetics* / Q000494:pharmacology; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D011336:Probability; D011817:Rabbits; D012307:Risk Factors; D012680:Sensitivity and Specificity
D008081:Liposomes; D005467:Floxuridine; D005472:Fluorouracil