pegfilgrastim的药代学和药效学。

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杨BB,城

pegfilgrastim的药代学和药效学。

Pharmacokinet。2011, (5): 295 - 306。doi: 10.2165 / 11586040-000000000-00000。

PubMed ID

21456630 (在PubMed

]

文摘

Pegfilgrastim白细胞生成素是一种持续阶段,一种methionyl重组人粒细胞集落刺激因子(g - csf),一个20 kDa聚乙二醇分子共价结合的氨基端蛋氨酸残渣。类似于白细胞生成素,pegfilgrastim增加中性粒细胞从承诺祖细胞的增殖和分化,诱导成熟,成熟的中性粒细胞和提高生存和功能,从而导致剂量依赖性增加中性粒细胞。皮下政府后,pegfilgrastim展品非线性药物动力学和接触pegfilgrastim增加dose-proportional方式,暗示的间隙pegfilgrastim随剂量增加而减小。白细胞生成素主要是消除肾脏和中性粒细胞/中性粒细胞前体;后者可能涉及到绑定的生长因子g - csf受体在细胞表面,通过内吞作用的生长因子受体复合物内化,和随后的细胞内降解。Pegylation的白细胞生成素呈现肾清除率微不足道,在双边施行肾切除术与肾功能损害受试者的老鼠和确认。因此,neutrophil-mediated pegfilgrastim消除间隙是主要的途径。在化疗所致嗜中性白血球减少症,pegfilgrastim结关的浓度显著降低,pegfilgrastim直到出现中性粒细胞持续复苏。Pegfilgrastim浓度在深刻的中性粒细胞减少患者持续更长时间。证据支持使用postnadir绝对中性粒细胞计数(ANC) > / = 1 x 109 / L作为替代指标阈值的间隙pegfilgrastim开始的水平。 After repeated administration of pegfilgrastim, the peak concentrations of pegfilgrastim decrease, likely due to increased neutrophil and neutrophil precursor mass. A pharmacokinetic-pharmacodynamic model was developed to describe the pharmacokinetic and ANC profiles of pegfilgrastim; the analysis supported that 100 mug/kg was an adequate weight-based dose of pegfilgrastim and predicted that 6 mg would be an optimal fixed dose of pegfilgrastim to simplify treatment. Data from a pivotal study confirmed that a once-per-chemotherapy-cycle injection of pegfilgrastim at 6 mg was as safe and effective as 11 daily injections of filgrastim at 5 mug/kg in reducing neutropenia and its complications in patients with breast cancer receiving four cycles of doxorubicin/docetaxel chemotherapy. Because of the highly efficient regulation of pegfilgrastim clearance via neutrophils and neutrophil precursors, a single fixed dose of pegfilgrastim can be given once per chemotherapy cycle in conjunction with a variety of myelosuppressive chemotherapy regimens.

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药物

Pegfilgrastim