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新型促红细胞生成剂:贫血管理的新时代。

Novel erythropoiesis-stimulating agents: a new era in anemia management.

作者信息

Macdougall Iain C

机构信息

Department of Renal Medicine, King's College Hospital, London, United Kingdom.

出版信息

Clin J Am Soc Nephrol. 2008 Jan;3(1):200-7. doi: 10.2215/CJN.03840907. Epub 2007 Dec 12.

Abstract

Nearly two decades ago, recombinant human erythropoietin transformed the management of chronic kidney disease anemia by allowing a more sustained increase in hemoglobin than was possible by intermittent blood transfusion. The treatment was highly effective, but because of the fairly short half-life of the molecule at approximately 6 to 8 h, injections usually had to be administered two to three times weekly. A second-generation erythropoietin analogue, darbepoetin alfa, was then created, with a longer elimination half-life in vivo that translated into less frequent dosing, usually once weekly or once every 2 wk. More recently, another erythropoietin-related molecule has been produced called Continuous Erythropoietin Receptor Activator with an even greater half-life, and other molecules are in development or are being licensed, including biosimilar epoetin products and Hematide. The latter is a synthetic peptide-based erythropoietin receptor agonist that, interestingly, has no structural homology with erythropoietin, and yet is still able to activate the erythropoietin receptor and stimulate erythropoiesis. The search goes on for orally active antianemic therapies, and several strategies are being investigated, although none is imminently available. This article reviews the latest progress with these novel erythropoietic agents in this new era in anemia management.

摘要

近二十年前,重组人促红细胞生成素改变了慢性肾脏病贫血的治疗方式,它能使血红蛋白水平实现比间歇性输血更持久的提升。这种治疗方法非常有效,但由于该分子的半衰期相当短,约为6至8小时,通常每周必须注射两到三次。随后,第二代促红细胞生成素类似物——阿法达贝泊汀问世,其在体内的消除半衰期更长,这意味着给药频率更低,通常为每周一次或每两周一次。最近,又研发出了另一种与促红细胞生成素相关的分子——持续促红细胞生成素受体激活剂,其半衰期更长,还有其他一些分子正在研发或已获许可,包括生物类似物促红细胞生成素产品和Hematide。后者是一种基于合成肽的促红细胞生成素受体激动剂,有趣的是,它与促红细胞生成素没有结构同源性,但仍能激活促红细胞生成素受体并刺激红细胞生成。人们仍在寻找口服活性抗贫血疗法,目前正在研究多种策略,不过尚无一种疗法即将问世。本文综述了在这个贫血治疗新时代这些新型促红细胞生成药物的最新进展。

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