Conversion of a novel 5-fluorouracil (5-FU) derivative to 5-FU in rats

The converting efficiency of a novel 5-FU derivative, 1, 3-didecanoyl-2-[6-[(5-fluorouracil-l-yl) carbonylamino] hexanoyl]glyceride (DFUG), to 5-FU was investigated in rat plasma. The degradation half-life of DFUG was 4.04 min when DFUG was incubated in rat plasma at 37 degrees C, though DFUG was considerably stable in buffers having different pH values, pH 1, 5 and 7.4. After iv administration, DFUG disappeared rapidly from rat plasma and considerable amount of 5-FU was detected in rat plasma. By comparing the AUC (area under the plasma 5-FU concentration vs. time curve from time zero to infinity) values with that obtained after iv injection of 5-FU, the fraction of 5-FU formed from DFUG was estimated to be about 80% in rats.