Pharmacokinetic modulation of plasma 5-fluorouracil concentrations to potentiate the antitumor activity of continuous venous infusion of 5-fluorouracil.

Abstract

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.

• Authors: S Fujii, M Fukushima, Y Shimamoto, T Shirasaka
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 80 Issue 6 Pg. 509-12 (Jun 1989) ISSN: 0910-5050 [Print] Japan
• PMID: 2503471 (Publication Type: Journal Article)

Chemical References

• Pyridines
• Tegafur
• 2,6-dihydroxy-3-cyanopyridine
• Uracil
• Fluorouracil

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Circadian Rhythm (drug effects)
• Drug Synergism
• Fluorouracil (administration & dosage, pharmacokinetics, therapeutic use)
• Infusions, Intravenous
• Kinetics
• Leukocyte Count
• Pyridines (administration & dosage, pharmacology)
• Rats
• Sarcoma, Yoshida (drug therapy)
• Tegafur (administration & dosage)
• Uracil (administration & dosage)