Title: Can Eniluracil Improve 5-Fluorouracil Therapy?
Abstract: account for much of the variability in the overall pharmacology of the pyrimidine antimetabolite drug 5-fluorouracil (5-FU; Table 1). This has included both intrapatient (circadian changes) as well as interpatient variations in pharmacokinetics and apparent bioavailability. DPD has also been shown to be a major factor in determining the variable host toxicity (with the extreme being complete deficiency of DPD with life-threatening toxicity) as well as antitumor efficacy (excessive DPD having been suggested to be a basis for 5-FU resistance). Lastly, although not well understood, it has been suggested that some toxicities associated with prolonged 5-FU use, eg, neurotoxicity, cardiotoxicity, and possibly hand-foot syndrome, may be due to 5-FU catabolites. For all of these reasons, it appeared logical for both experimental and clinical chemotherapists to target this critical step in 5-FU metabolism. Specific inhibition of DPD was hypothesized to be an effective mechanism by which much of the variability of 5-FU could be decreased, in turn, permitting 5-FU to be absorbed intact into the circulation after oral administration. Toxicity could be theoretically minimized by giving less 5-FU in this setting, and resistance that was due primarily to DPD overexpression in the tumor would potentially be reversed by the DPD inhibitor. The administration of a DPD inhibitor together with a source of 5-FU (as either 5-FU itself or as a prodrug) on a daily basis (typically as a b.i.d. or t.i.d. dose) over the course of several days up to almost a month was suggested as a means by which an orally administered 5-FU could potentially achieve some of the pharmacologic benefits of a 5-FU infusion. Over the years, numerous DPD in
Publication Year: 2002
Publication Date: 2002-05-01
Language: en
Type: letter
Indexed In: ['crossref', 'pubmed']
Access and Citation
Cited By Count: 4
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot