The relationship between plasma pharmacokinetics and tissue metabolites of 5-fluorouracil (5-FU) in patients with colorectal cancer.

To assess the relationship between the plasma pharmacokinetics of 5-Fluorouracil (5-FU) and the levels of intracellular 5-FU metabolites, we have studied eight patients presenting with primary carcinomas of the colon and rectum. Serum 5-FU levels and fluorinated metabolites within normal and malignant tissue were estimated using chromatographic methods. An analysis of the total fluorinated products against plasma halflife, plasma clearance and maximum plasma concentration failed to demonstrate any significant correlation. Furthermore the differing levels of 5-FU metabolites in normal and malignant tissue could not be correlated with the pharmacokinetic parameters studied. It is concluded that the cellular levels of active 5-FU metabolites reflect local cellular activity rather than the handling of the drug in vivo.