Influence of the administration of amifostine on the pharmacokinetics of 5-fluorouracil in patients with metastatic colorectal carcinoma

A high dose antineoplastic therapy with 5-fluorouracil (5-FU) is associated with severe side effects. It is thought that the cytoprotective drug amifo stine can reduce these side effects when it is given prior to a chemotherap eutic course. In this study, the pharmacokinetic parameters of 5-FU are mon itored in six patients, who received two chemotherapeutic courses of 2600 m g/m(2) BSA 5FU over 24 h, one course with 700 mg/m(2) BSA amifostine prior to the 5-FU infusion and the other without. 20 serum samples were drawn dur ing each infusion time and the 5-FU concentrations were determined by a sen sitive and selective GC-MS assay. The statistical analysis of the serum con centrations revealed no significant differences in the pharmacokinetic para meters of 5-FU, whether amifostine is administered or not. The conclusion c an be drawn that a reduction of side effects is due to the cytoprotective e ffect of amifostine and not to a change in the serum concentrations of 5-FU .