Pharmacokinetic modulation of plasma 5-fluorouracil concentrations to potentiate the antitumor activity of continuous venous infusion of 5-fluorouracil.
Methods for pharmacokinetic modulation of the plasma 5-fluorouracil (5-FU) level to increase antitumor activity during continuous venous infusion (CVI) of low doses of 5-FU were examined in Yoshida sarcoma-bearing rats. These methods were additional infusion of 5-FU for a short period (4 h) or oral administration of UFT or Tegafur during long-term CVI of 5-FU that alone gave a plasma 5-FU level of about 50 ng/ml. The antitumor effect on Yoshida sarcoma was markedly potentiated when an additive dose of 5-FU combined with 3-cyano-2,6-dihydroxypyridine (CNDP), a potent inhibitor of 5-FU degradation, giving a plasma level of about 500 ng/ml, was infused for 4 h. A similar increase in the antitumor effect was observed with oral administration of a conventional dose of UFT during CVI of 5-FU without CNDP, giving a plasma level of 30 to 60 ng/ml. These results suggest that the antitumor effect of CVI of 5-FU can be potentiated by pharmacokinetic modulation of the 5-FU concentration in the blood.
Fujii
S
S
Biwako Research Institute, Otsuka Pharmaceutical Co., Ltd., Shiga.
Fukushima
M
M
Shimamoto
Y
Y
Shirasaka
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000187:drug effects; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007700:Kinetics; D007958:Leukocyte Count; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012517:Sarcoma, Yoshida / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage
D011725:Pyridines; D005641:Tegafur; C053195:2,6-dihydroxy-3-cyanopyridine; D014498:Uracil; D005472:Fluorouracil