Pharmacokinetics of 5-fluorouracil: inter-relationship with biochemical kinetics in monitoring therapy.

The major difficulty in using pharmacokinetic concepts for monitoring individual therapy with 5-fluorouracil is based on the mostly intracellular location of the active nucleotide metabolites of 5-fluorouracil with no clear correlation of plasma levels of the drug. In addition, the basic biochemical mechanism of 'thymine-less cell death' following inhibition of de novo thymidylate synthesis by 2'-deoxy-5-flurouridine 5'-monophosphate (FdUMP) is poorly understood, and only some of the biochemical determinants of therapeutic response to 5-fluorouracil are known. Individualised therapy with 5-fluorouracil requires an intergrated approach which should include methods of pharmacokinetics and biochemical kinetics. 5-Fluorouracil stands as an example for most of the pyrimidine and purine metabolites to which similar consideration apply in monitoring of cancer chemotherapy.