title: Co-variables influencing 5-fluorouracil clearance during continuous venous infusion. A NONMEM analysis.
abstract: The objective of this study was to attempt to identify patient co-variables which could influence interpatient variability in 5-fluorouracil (5-FU) clearance during a 5-day continuous venous infusion (CVI, cisplatin 100 mg/m2 day 1 then 5-FU 1 g/m2/day days 2-6). The analysis was performed using a NONMEM program according to a linear one-compartment model. A total of 186 cycles (2 samples per day, 8 a.m. and 5 p.m.) were analysed from 104 patients with various cancers (the majority of head and neck and oesophagus). The study co-variables were age, sex, body surface area, hepatic metastases, peripheral mononuclear cell dihydropyrimidine dehydrogenase activity (PMNC-DPD), liver enzymes, clock-time (8 a.m. versus 5 p.m.), elapsed time during CVI. The data showed that 5-FU clearance was significantly reduced by increased age, low PMNC-DPD, high serum alkaline phosphatase and elapsed time during infusion. These data may be useful for improving knowledge of predictive factors which can influence 5-FU exposure and thus predispose to toxic manifestations.
authors.affiliation: Oncopharmacology Laboratory, Centre Antoine Lacassagne, Toulouse, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Etienne
authors.forename: E
authors.initials: E
authors.lastname: Chatelut
authors.forename: X
authors.initials: X
authors.lastname: Pivot
authors.forename: M
authors.initials: M
authors.lastname: Lavit
authors.forename: A
authors.initials: A
authors.lastname: Pujol
authors.forename: P
authors.initials: P
authors.lastname: Canal
authors.forename: G
authors.initials: G
authors.lastname: Milano
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D001830:Body Surface Area; D042943:Dihydrouracil Dehydrogenase (NADP); D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D012737:Sex Factors; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil