聚乙二醇非格司亭
中性粒细胞减少症
粒细胞集落刺激因子
医学
中性粒细胞绝对计数
菲格拉斯汀
化疗
药代动力学
环磷酰胺
药理学
粒细胞
体内
内科学
免疫学
胃肠病学
生物
生物技术
作者
Zheng Hu,Zhenjun Huang,Xiao Cen,Tao Wang,Kun Zhuang,Hong Zhou Yang,Dan Ping Zhang,Nai Sun,Rou Yun Sun,Li Wang,Yu Liang Huang,Xudong Yan
出处
期刊:Blood
[American Society of Hematology]
日期:2010-11-19
卷期号:116 (21): 1485-1485
被引量:5
标识
DOI:10.1182/blood.v116.21.1485.1485
摘要
Abstract Abstract 1485 Recombinant human granulocyte colony-stimulating factors (rhG-CSF) including filgrastim, lenograstim and pegfilgrastim are widely used to treat chemotherapy-induced neutropenia. However, it remains a challenge to manage severe neutropenia in cancer patients after high dose chemotherapy. The activation of G-CSFR by the G-CSF requires dimerization of two receptor chains bound to two G-CSF ligands. We hypothesized that a G-CSF dimer might generate a faster in vivo response, thus to benefit patients with severe neutropenia. F-627 is a recombinant human G-CSF dimer expressed in mammalian cells. In vitro, F-627 was able to activate STAT3 and to stimulate the proliferation of 32D-GCSFR and M-NSF60 cell lines. To evaluate the efficacy of F-627 in chemotherapy-induced neutropenia, 36 adult cynomolgus monkeys (3/sex) were injected with cyclophoshamide (CY, i.v., 60 mg/kg on day 0 and 65 mg/kg on day 1). Animals were randomized to receive (s.c.) either carrier, or F-627 on day 5 and day 10, at 25, 60 and 150 μg/kg, or rhG-CSF at 10 μg/kg /day (daily injection), or pegfilgrastim at 60 μg/kg on day 5 and day 10. Pharmacokinetics and pharmacodynamics (PK/PD) were evaluated. Significant absolute neutrophil count (ANC) increase was observed in animals treated with F-627 at 25 μg/kg compared to carrier-treated monkeys. At nadir, F-627 at 60 μg/kg generated optimal ANC response with 6.9- and 3.0-fold higher ANC compared to pegfilgrastim- (0.17 × 109/L) and rhG-CSF- (0.39 × 109/L) treated monkeys, respectively. The PK parameters of F627 at 60 ug/kg including MRT, Cmax, Tmax, AUC and CL were comparable to that of pegfilgrastim-treated monkeys, despite the relative G-CSF molar dose in F-627-treated animals was 2.5x lower than the pegfilgrastim-treated animals. The results demonstrate that the G-CSF dimer generated a faster response in CY-treated monkeys compared to the G-CSF monomer-treated animals, suggesting that F-627 could benefit cancer patients with severe neutropenia after high-dose chemotherapy. Disclosures: No relevant conflicts of interest to declare.
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