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调整用药建议以减少严重皮肤药物不良反应:一种药物基因组学方法。

Tailoring of recommendations to reduce serious cutaneous adverse drug reactions: a pharmacogenomics approach.

作者信息

Tan-Koi Wei Chuen, Sung Cynthia, Chong Yong Yeow, Lateef Aisha, Pang Shiu Ming, Vasudevan Archana, Aw Derrick, Lui Nai Lee, Lee Shan Xian, Ren Ee Chee, Koay Evelyn Sc, Tay Yong Kwang, Lim Yen Loo, Lee Haur Yueh, Dong Di, Loke Celine, Tan Liesbet, Limenta Michael, Lee Edmund Jd, Toh Dorothy, Chan Cheng Leng

机构信息

Health Products Regulation Group, Health Sciences Authority, 11 Biopolis Way, 11-03, Helios, Singapore 138667, Singapore.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

出版信息

Pharmacogenomics. 2017 Jun;18(9):881-890. doi: 10.2217/pgs-2017-0016. Epub 2017 Jun 8.

Abstract

The Health Sciences Authority launched a pharmacogenetics initiative in 2008 to facilitate evaluation of pharmacogenetics associations pertinent for Chinese, Malays and Indians in Singapore. The aim was to reduce the incidence and unpredictability of serious adverse drug reactions, with a focus on serious skin adverse drug reactions. This paper describes the gathering of evidence and weighing of factors that led to different genotyping recommendations for HLA-B15:02 with carbamazepine and HLA-B58:01 with allopurinol, despite both having strong genetic associations. Translation of pharmacogenomics at a national level requires careful deliberation of the prevalence of at-risk allele, strength of genetic associations, positive predictive value, cost-effectiveness and availability of alternative therapies. Our experience provides a perspective on translating genomic discoveries in advancing drug safety.

摘要

新加坡卫生科学局于2008年发起了一项药物遗传学倡议,以促进对与新加坡华人、马来人和印度人相关的药物遗传学关联进行评估。其目的是降低严重药物不良反应的发生率和不可预测性,重点关注严重皮肤药物不良反应。本文描述了证据的收集以及对各种因素的权衡,这些因素导致了对于卡马西平相关的HLA - B15:02和别嘌醇相关的HLA - B58:01得出不同的基因分型建议,尽管两者都有很强的遗传关联性。在国家层面进行药物基因组学的转化需要仔细考虑风险等位基因的流行率、遗传关联的强度、阳性预测值、成本效益以及替代疗法的可用性。我们的经验为在推进药物安全性方面转化基因组发现提供了一个视角。

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