Effects of the plasma concentration of 5-fluorouracil and the duration of continuous venous infusion of 5-fluorouracil with an inhibitor of 5-fluorouracil degradation on Yoshida sarcomas in rats.
The correlations of the 5-fluorouracil (5-FU) level in the plasma and the duration of continuous 5-FU infusion with the antitumor activity of 5-FU on Yoshida sarcomas in rats were examined. The circadian variation in the plasma level of 5-FU during continuous infusion was prevented by treatment with 3-cyano-2,6-dihydroxypyridine (CNDP), which strongly inhibits 5-FU degradation. On continuous venous infusion of 2 to 30 mg/kg of 5-FU over 24 h with CNDP at a molar ratio of 1:10 into normal rats, the 5-FU level in the blood was linearly proportional to the dose of 5-FU. The optimum schedule for antitumor activity on Yoshida sarcomas in rats was found to be infusion of 5-FU at 5 mg/kg over 24 h for 6 consecutive days, which gave a plasma 5-FU level of 176 ng/ml. Continuous infusion of 5-FU to give a plasma level of 300 ng/ml for 6 consecutive days from day 5 after implantation of tumor cells, when the tumors weighed about 1.0 g, resulted in complete regression of the tumors in all rats.
Fujii
S
S
Biwako Research Institute, Otsuka Pharmaceutical Co., Ltd. Shiga.
Shimamoto
Y
Y
Ohshimo
H
H
Imaoka
T
T
Motoyama
M
M
Fukushima
M
M
Shirasaka
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002940:Circadian Rhythm; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D009368:Neoplasm Transplantation; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D012517:Sarcoma, Yoshida / Q000188:drug therapy*
D011725:Pyridines; C053195:2,6-dihydroxy-3-cyanopyridine; D005472:Fluorouracil