5-fluorouracil and dihydropyrimidine dehydrogenase

Int J Clin Oncol. 2003 Jun;8(3):127-31. doi: 10.1007/s10147-003-0319-7.


Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme of (fluorinated) pyrimidine degradation that plays a significant role in the pharmacokinetics of 5-fluorouracil (5-FU). In addition, a catabolite of 5-FU induces a certain toxicity, and the sensitivity of 5-FU is determined by DPD activity in tumors. DPD is thus important clinically. Drugs have been developed that control variations of the pharmacokinetics of 5-FU by controlling or inhibiting DPD, thereby reducing toxicity and improving sensitivity. These fluorinated pyrimidines with DPD-inhibiting activity, called DPD-inhibitory fluoropyrimidines, contribute to oral therapy with 5-FU for cancer. This paper summarizes the important role of DPD in cancer chemotherapy with 5-FU.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil / pharmacology*
  • Fluorouracil / therapeutic use
  • Humans
  • Neoplasms / drug therapy
  • Oxidoreductases / metabolism
  • Oxidoreductases / pharmacology*
  • Sensitivity and Specificity
  • Structure-Activity Relationship


  • Antimetabolites, Antineoplastic
  • Oxidoreductases
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil