Effect of hemodialysis on the metabolic clearance of 5-fluorouracil in a patient with end-stage renal failure

A 64-year-old man on chronic hemodialysis for end-stage renal disease developed peritoneal carcinomatosis, and palliative chemotherapy with fluorouracil was started. The drug was administered (325 mg/m(2) as IV bolus, at 2 Pm) on 2 separate occasions, ie, 1 hour after dialysis and 2 days later, 49 hours after dialysis. The time course of the fluorouracil plasma concentration was determined, and the, main pharmacokinetic parameters were calculated. The slope of the monoexponential decay of plasma concentration was significantly greater I hour (0.161 minutes(-1)) than 49 hours after dialysis (0. 127 minutes'), and plasma clearance was correspondingly higher (1.78 L/min versus 1.46 L/min). The volume of distribution did not change (11.1 L versus 11.5 L). Because fluorouracil is minimally excreted by the renal route (about 10% of the dose) and is almost entirely metabolized by dihydropyrimidine dehydrogenase (DPD), it is suggested that plasma factors that accumulate during the interdialytic period and are removed by dialysis may inhibit DPD activity and, consequently, fluorouracil metabolic clearance.