摘要

Hypoxia-inducible factor prolyl hydroxylase inhibitors stabilize levels of hypoxia-inducible factor that upregulate transcription of multiple genes associated with the response to hypoxia, including production of erythropoietin. We conducted two phase 2a studies to explore the relationship between the dose of the hypoxia-inducible factor-prolyl hydroxylase inhibitor GSK1278863 and hemoglobin response in patients with anemia of CKD (baseline hemoglobin 8.5-11.0 g/dl) not undergoing dialysis and not receiving recombinant human erythropoietin (nondialysis study) and in patients with anemia of CKD (baseline hemoglobin 9.5-12.0 g/dl) on hemodialysis and being treated with stable doses of recombinant human erythropoietin (hemodialysis study). Participants were randomized 1:1:1:1 to a once-daily oral dose of GSK1278863 (0.5 mg, 2 mg, or 5 mg) or control (placebo for the nondialysis study; continuing on recombinant human erythropoietin for the hemodialysis study) for 4 weeks, with a 2-week follow-up. In the nondialysis study, GSK1278863 produced dose-dependent effects on hemoglobin, with the highest dose resulting in a mean increase of 1 g/dl at week 4. In the hemodialysis study, treatment with GSK1278863 in the 5-mg arm maintained mean hemoglobin concentrations after the switch from recombinant human erythropoietin, whereas mean hemoglobin decreased in the lower-dose arms. In both studies, the effects on hemoglobin occurred with elevations in endogenous erythropoietin within the range usually observed in the respective populations and markedly lower than those in the recombinant human erythropoietin control arm in the hemodialysis study, and without clinically significant elevations in plasma vascular endothelial growth factor concentrations. GSK1278863 was generally safe and well tolerated at the doses and duration studied. GSK1278863 may prove an effective alternative for managing anemia of CKD. 

译文

缺氧诱导因子脯氨酰羟化酶抑制剂稳定缺氧诱导因子水平,上调与缺氧反应相关的多个基因的转录,包括促红细胞生成素的产生。我们进行了两项 2a 期研究,以探索缺氧诱导因子-脯氨酰羟化酶抑制剂 GSK1278863 的剂量与 CKD 贫血患者血红蛋白反应 (基线血红蛋白 8.5-11.0g /dl) 不接受透析,不接受重组人促红细胞生成素 (非透析研究) 和 CKD 贫血患者(基线血红蛋白 9.5-12.0g/dl) 进行血液透析并接受稳定剂量的重组人促红细胞生成素治疗 (血液透析研究)。参与者被随机分为 1: 1,每日一次口服剂量的 GSK1278863 (0.5 毫克,2 毫克,或 5 毫克) 或对照组 (非透析研究的安慰剂; 继续使用重组人促红细胞生成素进行血液透析研究) 4 周,随访 2 周。在非透析研究中,GSK1278863 对血红蛋白产生剂量依赖性影响,在第 4 周,最高剂量导致平均增加 1g/dl。在血液透析研究中,在从重组人促红细胞生成素转换后,用 GSK1278863 治疗 5 毫克组维持平均血红蛋白浓度,而在低剂量组平均血红蛋白下降。在两项研究中,对血红蛋白的影响在通常在各自人群中观察到的范围内随着内源性促红细胞生成素的升高而出现,并且明显低于血液透析研究中重组人促红细胞生成素控制组的影响, 血浆血管内皮生长因子浓度无临床显著升高。GSK1278863 在所研究的剂量和持续时间下通常是安全的,耐受性良好。GSK1278863 可能是治疗 CKD 贫血的有效替代方法。

Prolyl Hydroxylase

消化 肝纤维化 临床研究术语
概述  :  

脯氨酰羟化酶(prolyl hydroxylase,PH)是胶原纤维合成酶,是肝纤维化的生化指标之一。肝脏纤维化胶原纤维合成亢进时,肝组织中及血清中PH活性均增高。 检测方法放射免疫法(RIA)。 正常值(20.8-58.2)μg/L。各实验室应建立自己适合的参考区间。 临床意义与评价用于肝脏纤维化的诊断、随访及预后判断。肝脏纤维化及伴有纤维化的肝脏病变时PH活性增高,如:(1)肝硬化及血吸虫性肝纤维化,PH明显增高;(2)原发性肝癌(多伴有肝硬化)PH增高,转

prolyl 英 [p'rɒlɪl] 美 [p'rɒlɪl]

释义   n. [生化] 脯氨酰;脯氨酰基

例句   Method: By the international literature, the structure-activity relationships of prolyl oligopeptidase inhibitors, natural active constituents, and clinical studies were summed up. 方法:根据国外相关文献,对脯氨酰寡肽酶抑制剂的构效关系、天然活性成分以及临床试验情况进行整理和归纳。

 

hydroxylase 英 [haɪ'drɒksɪleɪs] 美 [haɪ'drɒksɪleɪs]

释义   n. [生化] 羟化酶

例句   Objective: Clinical data of 19 Chinese patients with 21 hydroxylase deficiency (21OHD) were analyzed to improve the diagnosis and treatment level. 目的:分析19例21羟化酶缺陷症(21OHD)患者的临床和随访资料,提高该病的诊断和治疗水平。


请扫描右侧二维码,免费查看词汇专业知识背景