Clinical implications of dihydropyrimidine dehydrogenase on 5-FU pharmacology

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Abstract

Dihydropyrimidine dehydrogenase (DPD) is the initial rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU), accounting for catabolism of over 85% of an administered dose of 5-FU. DPD plays an important role in regulating the availability of 5-FU for anabolism. DPD also accounts for much of the variability observed with the therapeutic use of 5-FU. This includes variable 5-FU levels over 24 hours during a continuous infusion; the widely reported variability in the pharmacokinetics of 5-FU; the observed variable bioavailability that led to the recommendation that 5-FU not be administered as an oral agent; and lastly, the observed variability in both toxicity and drug response (resistance) after identical 5-FU doses. Knowledge of the DPD level, as well as the levels of other potentially important molecular markers (eg, thymidylate synthase), may permit adjustments or modulation of the 5-FU dose that can result in an increase in the therapeutic efficacy of 5-FU.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalOncology
Volume15
Issue number1 SUPPL. 2
StatePublished - Dec 1 2001

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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