Disposition of 5-fluorouracil during chronic hepatic arterial infusion to patients with carcinoma in the liver and effect on circulating platelets.
5-Fluorouracil was administered by continuous hepatic intra-arterial infusion to eight patients with the diagnosis of cancer of the gastrointestinal tract and hepatic metastases. Its elimination characteristics were investigated to see if they correlated with therapeutic effect or reduced clinical toxicity when the drug was given by this route. Urinary excretion of drug and metabolites was similar to findings after intravenous bolus doses. Disposition changes could not be correlated with therapeutic effect or clinical toxicity. A dose-related biphasic effect of 5-fluorouracil was found on circulating platelets. Doses greater than 6 mg kg-1 d-1 decreased the number of circulating platelets, while doses less than that resulted in an increase in circulating platelets. Further studies are required to determine the mechanism of the effect of 5-fluorouracil on platelets.
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D005472:Fluorouracil