5-FU-PEG-Liposomen zur intraaortalen Therapie. Ist die Metabolisierung von 5-Fluorouracil (5-FU) in Fluorourdesoxyuridin (FUDR) pH abhängig?

Abstract

A separate partial circulatory system with a defined flow via a roller pump is created by abdominal stop-flow therapy under hypoxic conditions. Forty chinchilla rabbits were subjected to intra-aortal (stop-flow therapy) or systemic therapy with 50 mg 5-FU or 5-FU-SUV-PEG liposomes. pH and pO₂ were measured at regular intervals during therapy. After 20 min, the concentration of 5-FU and its active metabolite 5-FURD were determined by HPLC in different organs. The 5-FURD concentration was measured in vitro in relation to the pH value. Subsequently, another 20 chinchilla rabbits received 50 mg of 5-FU or 5-FU-SUV-PEG liposomes intra-aortally (stop-flow therapy), keeping the pH value within the physiological range by NH3 titration, and the 5-FURD concentration was determined here as well. Intra-aortal applications of 5-FU-PEG liposomes increase 5-FU tumor concentrations 40-fold and para-aortal lymph-node concentrations 100-fold compared to i.v. applications. Metabolization of 5-FU to its active metabolite 5-FURD is strongly dependent on the pH value and can be modulated.