临床药物遗传学实施联盟指南：二氢嘧啶脱氢酶基因型与氟嘧啶类药物剂量。
Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing.
机构信息
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
出版信息
Clin Pharmacol Ther. 2013 Dec;94(6):640-5. doi: 10.1038/clpt.2013.172. Epub 2013 Aug 29.
Abstract
The fluoropyrimidines are the mainstay chemotherapeutic agents for the treatment of many types of cancers. Detoxifying metabolism of fluoropyrimidines requires dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene), and reduced or absent activity of this enzyme can result in severe, and sometimes fatal, toxicity. We summarize evidence from the published literature supporting this association and provide dosing recommendations for fluoropyrimidines based on DPYD genotype (updates at http://www.pharmgkb.org).
摘要
氟嘧啶类药物是治疗多种癌症的主要化疗药物。氟嘧啶类药物的解毒代谢需要二氢嘧啶脱氢酶（DPD，由 DPYD 基因编码），而这种酶的活性降低或缺失可能导致严重甚至致命的毒性。我们总结了已发表文献中的证据，支持这种关联，并根据 DPYD 基因型为氟嘧啶类药物提供剂量建议（更新于 http://www.pharmgkb.org）。
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Pharmacogenomics J. 2013 Oct;13(5):389-95. doi: 10.1038/tpj.2013.25. Epub 2013 Jul 16.
2
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Clin Pharmacol Ther. 2013 Jul;94(1):158-66. doi: 10.1038/clpt.2013.69. Epub 2013 Apr 3.
3
Phenotypic profiling of DPYD variations relevant to 5-fluorouracil sensitivity using real-time cellular analysis and in vitro measurement of enzyme activity.采用实时细胞分析和体外酶活性测定对与 5-氟尿嘧啶敏感性相关的 DPYD 变异进行表型谱分析。
Cancer Res. 2013 Mar 15;73(6):1958-68. doi: 10.1158/0008-5472.CAN-12-3858. Epub 2013 Jan 17.
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Dihydropyrimidine dehydrogenase (DPD) expression is negatively regulated by certain microRNAs in human lung tissues.二氢嘧啶脱氢酶（DPD）的表达在人肺组织中受到某些 microRNAs 的负调控。
Lung Cancer. 2012 Jul;77(1):16-23. doi: 10.1016/j.lungcan.2011.12.018. Epub 2012 Feb 3.
5
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Pharmacogenomics. 2011 Sep;12(9):1321-36. doi: 10.2217/pgs.11.72.
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