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 amifostine can reduce these side effects when it is given prior to a chemotherapeutic course. In this study, the pharmacokinetic parameters of 5-FU are monitored in six patients, who received two chemotherapeutic courses of 2,600 mg/m2 BSA 5FU over 24 h, one course with 700 mg/m2 BSA amifostine prior to the 5-FU infusion and the other without. 20 serum samples were drawn during each infusion time and the 5-FU concentrations were determined by a sensitive and selective GC-MS assay. The statistical analysis of the serum concentrations revealed no significant differences in the pharmacokinetic parameters of 5-FU, whether amifostine is administered or not. The conclusion can be drawn that a reduction of side effects is due to the cytoprotective effect of amifostine and not to a change in the serum concentrations of 5-FU.
Martens-Lobenhoffer
J
J
Institute of Clinical Pharmacology, Magdeburg, Germany.
Fuhlroth
J
J
Ridwelski
K
K
D000368:Aged; D004999:Amifostine / Q000008:administration & dosage / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000556:secondary*; D008297:Male; D008875:Middle Aged
D000964:Antimetabolites, Antineoplastic; D004999:Amifostine; D005472:Fluorouracil