Medizinische Universitätsklinik, Abt. Innere Medizin I, Hugstetter Strasse 55, Freiburg, Germany.
Ann Hematol. 2010 Sep;89(9):927-33. doi: 10.1007/s00277-010-0961-x. Epub 2010 Apr 29.
Recombinant human granulocyte colony-stimulating factor (filgrastim) has multiple hematologic and oncologic indications as Neupogen (Amgen filgrastim). Hospira has developed a biosimilar filgrastim (Nivestim). Here, results are reported from a phase I trial, primarily designed to compare the pharmacokinetic profiles of Hospira filgrastim and Amgen filgrastim. A phase I, single-center, open-label, randomized trial was undertaken to demonstrate equivalence of the pharmacokinetic characteristics of Hospira filgrastim and Amgen filgrastim. Forty-eight healthy volunteers were randomized to receive intravenous (i.v.) or subcutaneous (s.c.) dosing and then further randomized to order of treatment. Volunteers in each of the two dosing groups received a single 10microg/kg dose of Hospira filgrastim or Amgen filgrastim, with subsequent crossover. Bioequivalence was evaluated by analysis of variance; if the estimated 90% confidence intervals (CIs) for the ratio of 'test' to 'reference' treatment means were within the conventional equivalence limits of 0.80-1.25, then bioequivalence was concluded. Forty-six volunteers completed the study. Geometric mean area under the curve from time 0 to the last time point (primary endpoint) was similar in volunteers given Hospira filgrastim or Amgen filgrastim following i.v. (ratio of means: 0.96; 90% CI: 0.90-1.02) or s.c. (ratio of means: 1.02; 90% CI: 0.95-1.09) dosing; 90% CIs were within the predefined range necessary to demonstrate bioequivalence. Hospira filgrastim was well tolerated with no additional safety concerns over Amgen filgrastim. Hospira filgrastim is bioequivalent with Amgen filgrastim in terms of its pharmacokinetic properties and may provide a clinically effective alternative.
重组人粒细胞集落刺激因子（非格司亭）有多种血液学和肿瘤学适应证，作为 Neupogen（安进非格司亭）。贺斯哌开发了一种生物类似药非格司亭（Nivestim）。在这里，报告了一项 I 期临床试验的结果，该试验主要旨在比较贺斯哌非格司亭和安进非格司亭的药代动力学特征。进行了一项 I 期、单中心、开放标签、随机试验，以证明贺斯哌非格司亭与安进非格司亭的药代动力学特征具有等效性。48 名健康志愿者被随机分配接受静脉（i.v.）或皮下（s.c.）给药，然后进一步随机分配治疗顺序。每个给药组的志愿者均接受单次 10μg/kg 的贺斯哌非格司亭或安进非格司亭，随后进行交叉。通过方差分析评估生物等效性；如果“试验”与“对照”治疗均值的比值的估计 90%置信区间（CI）在 0.80-1.25 的传统等效范围内，则得出生物等效性的结论。46 名志愿者完成了研究。静脉注射（i.v.）（均值比：0.96；90%CI：0.90-1.02）或皮下（s.c.）（均值比：1.02；90%CI：0.95-1.09）给药后，给予贺斯哌非格司亭或安进非格司亭的志愿者的曲线下面积从 0 到最后时间点的几何均数（主要终点）相似；90%CI 在证明生物等效性所需的预定范围内。与安进非格司亭相比，贺斯哌非格司亭耐受性良好，没有额外的安全性问题。贺斯哌非格司亭在药代动力学特性方面与安进非格司亭具有生物等效性，可能提供一种有效的临床替代药物。
