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5-fluorouracil and dihydropyrimidine dehydrogenase
1Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. tkubota@sc.itc.keio.ac.jp
Abstract:
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.
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