DEACYLATION REACYLATION CYCLE - A POSSIBLE ABSORPTION MECHANISM FOR THE NOVEL LYMPHOTROPIC ANTITUMOR AGENT DIPALMITOYLPHOSPHATIDYLFLUOROURIDINE IN RATS

Dipalmitoylphosphatidylfluorouridine (DPPF) is a potent antitumor agen t that selectively gains access to the lymphatic system. To determine whether DPPF enters the lymph in an unmodified form, we administered D PPF orally to rats and analyzed lymph collected from a cannula in the thoracic duct. Although lymph was found to contain only very low level s of DPPF, two congeners of DPPF were detected at high levels. Instrum ental analysis demonstrated that these congeners are -palmitoyl-2-arac hidonoylphosphatidylfluorouridine (PAPF) and 1-palmitoyl-2-linoleoyl-p hosphatidylfluorouridine (PLPF). PAPF and PLPF levels in thoracic lymp h were shown to be approximately 30 times higher than those in plasma. These results suggest that DPPF is absorbed from the intestinal tract via the deacylation-reacylation cycle for the uptake of phospholipids and is selectively delivered to the lymphatic route after oral admini stration. DPPF is a candidate drug for the treatment of tumor metastas is, especially in cases where metastasis has occurred via the lymphati c route.