A comparison of the safety margins of botulinum neurotoxin serotypes A, B, and F in mice
A comparison of the safety margins of botulinum neurotoxin serotypes A, B, and F in mice
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DOI：
10.1016/s0041-0101(01)00101-5
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发表时间：
2001-12-01
期刊：
影响因子：
2.8
通讯作者：
Aoki, KR
中科院分区：
文献类型：
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作者：
Aoki, KR
这项研究比较了A型肉毒毒素(BTX)的两种制剂和B型和F型肉毒毒素(BTX)各一种制剂在小鼠肌肉内的安全边际。小鼠接受BTX-A(肉毒杆菌(R)或DySPORT(R))的肌注(0-200U kg(-1)体重)、BTX-B的实验制剂(Wako Chemals，Inc.)或BTX-F的实验制剂(Wako)。一名戴着面具接受治疗的观察者使用数字外展评分(DAS)测试对肌肉无力进行评分。绘制DAS响应峰值并计算IM ED50值。每种BTX制剂的安全边际计算为后肢注射后的IM半数致死剂量与DAS试验中的半数有效剂量(IM LD50/IM ED50)的比率。每种制剂(10只小鼠/剂量)重复实验4-6次。BTX-F(WAKO；16.7+/-3.9)和一种BTX-A制剂(肉毒杆菌(R)；13.9+/-1.7)的平均安全边际值最高。另一种BTX-A制剂(DySPORT(R))和BTX-B(WAKO)的平均安全边际值显著较低(分别为7.6+/-0.9和4.8+/-1.1)。因此，BTX制剂在小鼠身上表现出不同的安全边际。这些结果支持这样的假设，即这些制剂是独特的疗法，不能基于简单的剂量比进行互换。(C)2001爱思唯尔科学有限公司。保留所有权利。
This study compared the respective intramuscular (IM) safety margins of two preparations of botulinum toxin (BTX) serotype A and one preparation each of BTX serotypes B and F in mice. Mice received an IM injection (0-200 U kg(-1) body weight) of BTX-A (BOTOX(R) or DYSPORT(R)), an experimental preparation of BTX-B (WAKO Chemicals, Inc.), or an experimental preparation of BTX-F (WAKO). An observer who was masked to treatment scored muscle weakness using the Digit Abduction Scoring (DAS) assay. Peak DAS responses were plotted and IM ED50 values calculated. The safety margin for each BTX preparation was calculated as a ratio of the IM median lethal dose after hind limb injection to the median effective dose in the DAS assay (IM LD50/IM ED50). Experiments were repeated 4-6-times for each preparation (10 mice/dose). Mean safety margin values were highest for BTX-F (WAKO; 16.7 +/- 3.9) and one of the BTX-A preparations (BOTOX(R); 13.9 +/- 1.7). Mean safety margins values for the other BTX-A preparation (DYSPORT(R)) and BTX-B (WAKO) were significantly lower (7.6 +/- 0.9 and 4.8 +/- 1.1, respectively). Thus, the BTX preparations exhibited different safety margins in mice. These results support the hypothesis that the preparations are unique therapeutics and are not interchangeable based on a simple dose ratio. (C) 2001 Elsevier Science Ltd. All rights reserved.