Botulinum neurotoxin serotypes A and B preparations have different safety margins in preclinical models of muscle weakening efficacy and systemic safety
Botulinum neurotoxin serotypes A and B preparations have different safety margins in preclinical models of muscle weakening efficacy and systemic safety
复制标题
DOI：
10.1016/s0041-0101(02)00086-7
复制
发表时间：
2002-07-01
期刊：
影响因子：
2.8
通讯作者：
Aoki, KR
中科院分区：
文献类型：
--
作者：
Aoki, KR
这项临床前研究比较了最近批准的B型肉毒杆菌毒素（BTX-B B; Myobloc（TM）/Neurobloc（TM））与A型肉毒杆菌毒素（BTX-A; BOTOX（R））的肌肉弱化功效、持续时间和安全范围。小鼠接受BTX-B（1 - 150 U/kg）或BTX-A（1 - 120 U/kg）的单后肢肌内注射。对治疗设盲的观察者使用手指外展评分试验在0-4量表上评估肌肉减弱疗效的幅度和持续时间。安全范围确定为IM半数致死剂量与在DAS中产生半数最大肌无力的IM剂量的比值。BTX-A在比BTX-B更低的剂量下产生肌无力（IM ED 50：分别为6.2 +/- 0.6对20.8 +/-1.4U/kg）（p < 0.0001）。29 U/kg的BTX-A和67 U/kg的BTX-B产生了接近4的可比较的峰值DAS评分，表明最大肌无力。在这些剂量下，BTX-A的持续时间更长，与BTX-B在第14天恢复到基线相比，BTX-A在第36天恢复到基线。在50%的小鼠中致死的BTX-A的平均剂量低于BTX-B（分别为81.4 +/- 3.5对104.6 +/- 1.9 U/kg）（p < 0.001），并且安全界限更高（分别为13.9 +/- 1.7对5.4 +/- 0.3（p < 0.001）。这些结果表明，肌肉弱化功效的BTX-A：BTX-B剂量比不同于IM注射后全身效应的比例，并表明没有单一剂量比足以比较这些制剂。发现的体内差异与这两种产品报告的不同临床特征一致。(C)2002爱思唯尔科技有限公司。保留所有权利。
This preclinical study compared the muscle weakening efficacy, duration, and safety margin of the recently approved botulinum toxin type B (BTX-B; Myobloc(TM)/Neurobloc(TM)) to botulinum toxin type A (BTX-A; BOTOX(R)). Mice received a single hind limb intramuscular injection of BTX-B (1 - 150 U/kg) or BTX-A (1 - 120 U/kg). An observer who was masked to treatment assessed the magnitude and duration of muscle weakening efficacy on a 0-4 scale using the digit abduction scoring assay. Safety margins were determined as the ratio of the IM median lethal dose to the IM dose that produced half-maximal muscle weakness in the DAS. BTX-A produced muscle weakness at lower doses than BTX-B (IM ED50: 6.2 +/- 0.6 vs. 20.8 +/- 1.4 U/kg, respectively) (p < 0.0001). BTX-A at 29 U/kg and BTX-B at 67 U/kg produced comparable peak DAS scores of approximate to4 indicating maximal muscle weakness. At these doses, the duration of BTX-A was longer, with a return to baseline by day 36 compared to a return to baseline by day 14 with BTX-B. The mean dose that was lethal in 50% of mice was lower for BTX-A than BTX-B (81.4 +/- 3.5 vs. 104.6 +/- 1.9 U/kg, respectively) (p < 0.001) and the safety margin was higher (13.9 +/- 1.7 vs. 5.4 +/- 0.3, respectively (p < 0.001). These results indicate that the BTX-A:BTX-B dose ratio for muscle weakening efficacy is different from the ratio for systemic effects following IM injections and suggest that no single dose ratio is adequate to compare these preparations. The in vivo differences found are consistent with the different clinical profiles reported for these two products. (C) 2002 Elsevier Science Ltd. All rights reserved.