BIOCHEMICAL AND CLINICAL-PHARMACOLOGY OF 5-FLUOROURACIL

The cellular and clinical pharmacology of fluoropyrimidines is charact erized by marked interpatient variability in tumor response and patien t tolerance. Understanding the metabolic pathways followed by 5-fluoro uracil (5-FU) has led to new, strategies to optimize therapy with thes e important agents. The ''fluoropyrimidine phenotype'' of tumor cells cml be used to determine whether therapy with these agents is appropri ate and if so, whether one fluoropyrimidine may offer a particular adv antage over another. Combining a dihydropyrimidine dehydrogenase inhib itor with 5-FU offers the potential to minimize pharmacokinetic variab ility and, in that way, to improve oral bioavailability,facilitate dos age adjustment to achieve desired concentrations, and increase the lik elihood of tumor response while minimizing the risk of severe toxicity to individual patients.