Clinical Trial to Investigate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Recombinant Factor VIIa in Japanese Patients With Hemophilia With Inhibitors
Clinical Trial to Investigate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Recombinant Factor VIIa in Japanese Patients With Hemophilia With Inhibitors
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研究重组 VIIa 因子在日本血友病患者体内的药代动力学、药效学、安全性和疗效的临床试验
DOI：
10.1007/bf02994016
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发表时间：
2001
影响因子：
2.1
通讯作者：
H. Saito
中科院分区：
文献类型：
--
作者：
A. Shirahata;T. Kamiya;J. Takamatsu;T. Kojima;K. Fukutake;M. Arai;H. Hanabusa;H. Tagami;A. Yoshioka;M. Shima;H. Naka;S. Fujita;Y. Minamoto;J. Kamizono;H. Saito
一项多中心、开放标签的人类重组因子VIIa （rFVIIa）临床试验在日本严重血友病A或B患者中进行。试验由两部分组成。在研究1中，对8例患者单次给药120 μg/kg的rfviia的药代动力学、药效学和安全性进行了研究。在随后的研究2中，我们对10例患者进行了为期24周的止血效果和安全性评估。在研究1中，发现平均最大FVII凝血活性（FVII:C）发生在10分钟后；然后，活性迅速下降，并在单次静脉输注rFVIIa后24小时内恢复到基线。FVII:C的平均半衰期为3.5小时。患者的活化部分凝血活酶时间和凝血酶原时间立即缩短，但在给药后24小时内恢复到基线水平。在研究2中，10例患者给予86 ~ 120 μg/kg（平均97 μg/kg） rfviia 1 ~ 85次。58.0%（91/157）的出血发作得到良好或有效治疗，5例（3.2%）出血发作无效。止血效果与出血部位、平均剂量、注射次数的关系无明显趋势。然而，3小时内治疗的有效率（90.0%）明显高于间隔较长时间治疗的有效率（31.0%）。没有观察到与治疗相关的不良事件，也没有证据表明对rFVIIa产生抗体。总之，rFVIIa是治疗血友病患者出血发作抑制剂的有效且耐受性良好的选择。
A multicenter and open-labeled clinical trial of human recombinant factor VIIa (rFVIIa) was conducted in Japanese patients with severe hemophilia A or B with inhibitors. The trial consisted of 2 parts. In study 1, the pharmacokinetics, pharmacodynamics, and safety of a single dose of 120 μg/kg ofrFVIIa were investigated in 8 patients. In the subsequent study 2, the hemostatic effect and safety ofrFVIIa were evaluated during a 24-week period in 10 patients. In study 1, the mean maximum FVII-coagulant activity (FVII:C) was found to occur after 10 minutes; activity then decreased rapidly and returned to the baseline within 24 hours after a single intravenous infusion of rFVIIa. The mean half-life of FVII:C was 3.5 hours. The activated partial thromboplastin time and prothrombin time in the patients were immediately shortened but returned to the baseline within 24 hours after dosing. In study 2, 86 μg/kg to 120 μg/kg ofrFVIIa (mean, 97 μg/kg) was administered 1 to 85 times to 10 patients. A total of 58.0% (91/157) of bleeding episodes were treated excellently or effectively, with 5 (3.2%) ineffective episodes. There was no apparent trend in the relationship of the hemostatic effect with bleeding sites, mean dose, or number of injections. The efficacy rate, however, was significantly higher (90.0%) in bleeding episodes treated within 3 hours than in those treated at longer intervals (31.0%). No treatment-related adverse events were observed, and there was no evidence of antibody formation to rFVIIa. In conclusion,rFVIIa is an effective and well-tolerated option for treatment of bleeding episodes in hemophilia patients with inhibitors.
DOI：
10.1073/pnas.83.8.2412
发表时间：
1986-04-01
影响因子：
11.1
作者：
HAGEN, FS;GRAY, CL;DAVIE, EW
通讯作者：
DAVIE, EW