Abstract
Tegafur(Futraful, FT)is well absorbed from GI tract, and metabolized to 5-FU mainly in the liver microsomal enzyme, P-450. Biochemical modulation of FT was attempted to enhance 5-FU delivery in tumor tissues by mean of the increase in 5-FU production from FT and the inhibition of the catabolism of produced 5-FU, and the pharmnacokinetics were investigated in S. 180 bearing mice and VX2 bearing rabbits. Phenobarbital (PB) +glutathione+FT : PB is known as an inducer of P-450. This combination resulted a higher level of 5-FU in the blood and tissues. Uracil(U)+FT ; UFT : U inhibits an inactivating enzyme of 5 FU, dihydrouracil dehydrogenase. In an appropriate dose of UFT, 5-FU level in tumor was selectively elevated. 5-chloro-2, 4-dihydroxypyridine (CDHP)+Oxonic acid(Oxo)+FT ; S-1 : CDHP inhibits the catabolism of 5-FU by dihydrouracil dehydrogenase very strongly and enhanced 5-FU level especially in tumor tissues. Oxo persisted in GI tract and inhibits the anabolism of 5-FU, and protected GI toxicities.
