Puzzles in the clinical pharmacokinetics of fluorouracil

The pharmacokinetics of fluorouracil (5FU) were studied in two groups of pa tients, the administration of 105 i.v. as daily bolus (x5) or 5-day continu ous infusions. The 5FU pharmacokinetics were extremely variable from day to day, i.e. from one bolus to the next or during the continuous infusion, es pecially in some patients. The variations were lower for the daily bolus, b ut still remained high. The pharmacokinetics of cisplatin, given simultaneo usly during continuous infusions did not show the same variability; therefo re the variability could be specific for 5FU. The role of implantable subcu taneous ports as the most probable source of this extraordinary variability is discussed. We hypothesise that in some patients the implantable subcuta neous 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.