Relative importance of dose, body surface area, sex, and age for 5-fluorouracil clearance.
The pharmacokinetics of 5-fluorouracil (FU) has been investigated in 26 cancer patients; 15 of these patients were pretreated with methotrexate (MTX). FU was given by a constant rate intravenous infusion within 10 min, at doses of 320-960 mg/m2. Total plasma clearance, beta-half-life, and steady-state distribution volume were determined with 43 treatments, based on plasma level measurements up to 90 min after the end of the infusion. Average clearance decreased from 1.3 l/min for 320 to 0.7 l/min for 960 mg FU/m2. Multiple linear regression calculations with dose, body surface area, sex, age, and MTX pretreatment as independent variable and clearance as dependent variable confirmed the dependency of clearance on dose and body surface area but also showed that, with equal FU dose per m2, clearance was higher in males than in females, on the average, by 0.22 l/min. There was also suggestive (although not significant) evidence of a (reducing) influence of age on FU clearance.
Port
R E
RE
Deutsches Krebsforschungszentrum, Institute of Biochemistry, Heidelberg, FRG.
Daniel
B
B
Ding
R W
RW
Herrmann
R
R
D000328:Adult; D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001830:Body Surface Area; D001943:Breast Neoplasms / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D012004:Rectal Neoplasms / Q000188:drug therapy; D012727:Sex Characteristics
D005472:Fluorouracil; D008727:Methotrexate