DPD 催化 5-FU 和尿嘧啶转化为 5,6-二氢尿嘧啶,这一过程是 5-FU 代谢的速率限制步骤。该酶的活性直接影响 5-FU 的药物浓度和疗效,因此,DPD 的缺陷可能导致 5-FU 在体内的积累,从而导致毒性反应增加[2]。此外,DPD 的活性与患者对化疗的反应...
美国食品药品监督管理局(FDA)发布了一项通知,旨在提高对卡培他滨和氟尿嘧啶(5-FU)治疗相关的二氢嘧啶脱氢酶(DPD)缺陷风险的认识。所有医疗服务提供者应当在治疗前告知患者,DPD缺乏可能导致严重甚至危及生命的副作用,并与患者讨论是否进行DPD...
该研究对患者的U值、UH2/U比值、基因型特征以及5-FU的代谢情况进行了详细的数据分析。结果显示，患者的U值或UH2/U比值与DPYD基因型缺乏之间并未发现紧密关系，这与先前的研究结果形成对比。同时，该研究还首次指出，5-FU的清除率与DPYD基因型之间也缺乏相关性。然而，该研究的一个重要发现是，当U值或UH2/U比值...
2. Launay, M., et al.,Upfront Dpd Deficiency Detection to Secure 5-Fu Administration: Part 2- Application to Head-and-Neck Cancer Patients.Clin Cancer Drugs, 2017.4(2): p. 122-128. 3. Caudle, K.E., et al.,Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine...
DPD deficiency is a pharmacogenetics syndrome associated with severe/lethal toxicities upon 5-FU or capecitabine intake. We have developed a simple, rapid, and inexpensive functional testing for DPD activity, as a means to identify deficient patients and to anticipate subsequent 5-FU-related ...
This is the initial and rate-limiting enzyme in the catabolic pathway and therefore a partial or complete DPD deficiency is associated with different degrees of 5-FU toxicity whose most frequent manifestations include neutropenia, mucositis and diarrhoea [2]. 展开 ...
In 5-FU-based cancer chemotherapy, severe toxicities were... K Omura - 《International Journal of Clinical Oncology》 被引量: 151发表: 2003年 Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil admin... ...
Impaired 5FU degradation, through low DPD activity, has led to severe, life-threatening or fatal toxicity after administration of 5FU. Complete DPD deficiency is associated with the inherited metabolic disease thymine uraciluria. Several mutations in the gene encoding DPD have recently been identified...
Furthermore, the frequency of DPD deficiency has been estimated to be as high as 2 – 3% (Etienne et al, 1994; Lu et al, 1995; Chazal et al, 1996). To date, a direct correlation between DPYD gene mutation and decreased 5-FU clearance has only been suggested but never been proven. ...
The main origin of FU-related toxicities is a deficiency of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme of 5-FU catabolism. DPD deficiency may be identified through pharmacogenetics testing including phenotyping (direct or indirect measurement of enzyme activity) or genotyping (...