Puzzles in the clinical pharmacokinetics of fluorouracil.
The pharmacokinetics of fluorouracil (5FU) were studied in two groups of patients, the administration of 105 i.v. as daily bolus (x5) or 5-day continuous infusions. The 5FU pharmacokinetics were extremely variable from day to day, i.e. from one bolus to the next or during the continuous infusion, especially in some patients. The variations were lower for the daily bolus, but still remained high. The pharmacokinetics of cisplatin, given simultaneously during continuous infusions did not show the same variability; therefore the variability could be specific for 5FU. The role of implantable subcutaneous ports as the most probable source of this extraordinary variability is discussed. We hypothesise that in some patients the implantable subcutaneous ports used for 5FU infusion, could cause transient and extremely high plasma concentrations, exacerbated by the very short half life of the drug and by saturation of its catabolism.
Desoize
B
B
IFR53-EA2063, Laboratoire de Biochimie, Reims, France. bernard.desoize@univ-reims.fr
Bouche
O
O
Berthiot
G
G
Coninx
P
P
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy*; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil