[5-fluorouracil and dihydropyrimidine dehydrogenase].
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the (fluoro) pyrimidine catabolic pathway, and has an important role in 5-fluorouracil (5-FU) pharmacology. Some studies have demonstrated that the fluoropyrimidine catabolite may be related to the toxicity of 5-FU, and tumoral DPD prescribes the response to 5-FU-based therapy. By controlling DPD activity, a new class of fluorinated pyrimidines have been developed to minimize the variability of 5-FU pharmacodynamics, to decrease 5-FU toxicity, and improve its efficacy. Recently, these drugs, referred to as DIFs (DPD inhibitory fluoropyrimidines), have brought us to a new era of oral 5-FU therapy. The importance of DIF in 5-FU-based therapy is reviewed herein.
Kubota
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Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP); D004338:Drug Combinations; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D010088:Oxidoreductases / Q000235:genetics / Q000502:physiology*; D010094:Oxonic Acid / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D005641:Tegafur / Q000627:therapeutic use; D014498:Uracil / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D014498:Uracil; D010094:Oxonic Acid; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil