Potentiation of the antitumor effect of 5-fluoro-2'-deoxyuridine esters in combination with acyclothymidine esters on L1210 in mice via oral administration

J Pharm Sci. 1988 Nov;77(11):939-43. doi: 10.1002/jps.2600771108.

Abstract

Fifteen pyrimidine-related compounds were evaluated for their ability to inhibit enzymatic degradation of 5-fluoro-2'-deoxyuridine (FUdR). Acyclothymidine [5-methyl-1-(2'-hydroxyethoxymethyl)uracil] showed the highest inhibitory effect on the phosphorolytic degradation of FUdR in various tissue homogenates derived from mouse, rat, and beagle organs. Both the drug (FUdR) and the inhibitor (acyclothymidine) were esterified with appropriate aliphatic acids in order to synchronize their behavior after simultaneous oral administration. The antitumor activity of orally administered FUdR esters was potentiated by the simultaneous oral administration of the acyclothymidine esters, but not by acyclothymidine.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Chemical Phenomena
  • Chemistry, Physical
  • Dogs
  • Drug Synergism
  • Floxuridine / administration & dosage
  • Floxuridine / analogs & derivatives*
  • Floxuridine / antagonists & inhibitors
  • Floxuridine / pharmacology*
  • Leukemia L1210 / drug therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Pyridines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Species Specificity
  • Uracil / administration & dosage
  • Uracil / analogs & derivatives*
  • Uracil / pharmacology

Substances

  • Antineoplastic Agents
  • Pyridines
  • Floxuridine
  • Uracil
  • N-(2-(hydroxyethoxy)methyl)-5-methyluracil