Some patients treated with 5-fluorouracil (5-FU) metabolize the drug slowly and are at risk for excessive toxicity. Bocci et al used a trial dose of 5-FU to determine kinetic parameters in a patient prior to starting a regular course of therapy. The authors are from the University of Pisa, General Hospital Lucca and General Hospital Livorno in Italy.


Primary metabolite for 5-FU: 5-fluor-5,6-dihydrouracil (5-FDHU)


Metabolic system: dihydropyrimidine dehydrogenase (DPD)


Patients who are deficient in DPD will be slow metabolizers of 5-FU and are more likely to experience serious toxicity. Slow metabolism does not explain all cases of severe toxicity but does identify an important group.


Protocol: test dose 5-FU 250 mg per square meter body surface area


Pharmacokinetic parameters determined:

(1) half-life (beta phase) 5-FU in hours

(2) total body clearance of 5-FU in liters per hour per square meter

(3) time to 5-FDHU peak concentration in minutes



Slow Metabolizers

5-FU half-life (beta)

0.16 +/- 0.15 hours

> 5 hours

total body clearance

65.7 +/- 32 L per h per sq m

< 1 liter per h per sq m

time to peak 5-FDHU

27 +/- 10 minutes

>= 45 minutes


A patient suspected of slow metabolism was treated with irinotecan instead.


An assay for DPD activity in peripheral blood mononuclear cells can be performed but is difficult to perform reliably and may not be readily available.


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