Plasma, intestine and tumor levels of 5-fluorouracil in mice bearing L1210ascites tumor following oral administration of 5-fluorouracil, UFT (Mixed compound of tegafur and uracil), carmofur and 5 '-deoxy-5-fluorouridine

Several 5-fluorouracil (5-FU) derivatives, 1-hexylcarbamoyl-5-fluorouracil (HCFU), 5 ' -deoxy-5-fluorouridine (5 ' -DFUR) and UFT (mixed compound of t egafur and uracil), have been developed and clinically widely used. However , comparative pharmacokinetic studies of the parent compound and other fluo rinated drivatives have not been precisely reported. The dosage of the oral clinical use for human cancer of 5-FU, HCFU, 5 ' -DFUR and UFT as tegafur (FT) is 200-300 mg/d, 600 mg/d, 800-1200 mg/d and 300-600 mg/d respectively . These amounts of the drugs are almost equimolar. Previously, we reported the effect of oral equimolar administration of each four drugs on thymidila te synthase activity, deoxyribonucleotide metabolism and cell cycle progres sion in L1210 ascites tumor.(1.2)) In this study, we examined the antitumor effect and 5-FU concentration in the plasma, intestine and tumor after ora l equimolar administrations of each drug using BDF1 mice bearing L1210 asci tes tumor. In our study, UFT showed the best life prolongation among these four drugs. The intestine 5-FU level was highest by treatment with 5-FU dur ing the initial 4 h. The plasma 5-FU level was highest by treatment with HC FU for 4 h. But the tumor 5-FU level was highest by treatment with UFT over the 24 h. In spite of the high plasma 5-FU concentration after the treatme nt with HCFU, the 5-FU concentration in the tumor was below the detectable level until 24 h. These findings suggested that the highest specific accumu lation of 5-FU in tumor cells may explain the best therapeutic results of U FT.