Pelvipharm, Orsay, France.
Eur Urol. 2012 May;61(5):1054-61. doi: 10.1016/j.eururo.2012.01.051. Epub 2012 Feb 8.
Two botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not interchangeable.
Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord-injured (SCI) rats with NDO.
DESIGN, SETTING, AND PARTICIPANTS: Female, adult, Sprague-Dawley rats (n=98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25μl injected, eight sites) of vehicle (V); Dysport 2, 5, 7.5, 10, and 12.5 U; and Botox 0.8, 2, 5, 7.5, and 10 U. Two days after injection, continuous cystometry was performed in conscious rats.
Voiding contractions (VC) were assessed by duration of VC, intercontraction interval, voided volume, maximal pressure, pressure threshold change, and intravesical baseline pressure (BP), while nonvoiding contractions (NVC) were evaluated by amplitude, frequency, and volume threshold to elicit NVC. MEDs for Dysport and Botox were determined by analysis of variance step-down trend test.
MEDs for Dysport and Botox were 10 U and 7.5 U, respectively. Regarding VC, only BP significantly decreased after 10 U Dysport and 7.5 U Botox compared to V (from 3.7±0.6 to 1.5±0.1 and 1.4±0.3mm Hg, respectively; p<0.01 and p<0.001, respectively). Dysport (10 U) and Botox (7.5 U) significantly inhibited NVC by decreasing their amplitude (from 7.4±1.1 to 5.8±0.5 and 5.4±0.6mm Hg, respectively; p<0.05); frequency (from 2.2±0.4 to 1.5±0.2 and 1.3±0.3 NVC per minute, respectively; p<0.01); and increasing volume threshold to elicit NVC (from 29.8±3.7 to 47.6±6.9 and 47.7±6.3%, respectively; p<0.05 and p<0.001, respectively).
This is the first preclinical dose-ranging study with Dysport and Botox under standardized conditions showing similar inhibiting effects on NDO, albeit at different MEDs. It highlights the importance of distinguishing each preparation for predicted outcomes and doses to be used. Further studies in patients with NDO are warranted to confirm these experimental results.
两种 A 型肉毒毒素已被评估用于治疗人类难治性神经源性逼尿肌过度活动（NDO）：Dysport（阿博特毒素 A）和 Botox（肉毒毒素 A）。然而，这两种不同的商业化产品具有不同的效价单位，不能互换。
评估 Dysport 和 Botox 在患有 NDO 的脊髓损伤（SCI）大鼠中的剂量反应，并确定最小有效剂量（MED）。
设计、地点和参与者：雌性成年 Sprague-Dawley 大鼠（n=98）接受 T8-T9 脊髓横断。脊髓损伤后 19 天，大鼠接受膀胱内注射（25μl 注射，8 个部位）的载体（V）；Dysport 2、5、7.5、10 和 12.5 U；和 Botox 0.8、2、5、7.5 和 10 U。注射后两天，在清醒大鼠中进行连续膀胱测压。
通过 VC 的持续时间、收缩间期、排空量、最大压力、压力阈值变化和膀胱内基础压力（BP）评估逼尿肌收缩（VC），而通过幅度、频率和产生 NVC 的体积阈值评估非逼尿肌收缩（NVC）。通过方差逐步下降趋势检验确定 Dysport 和 Botox 的 MED。
Dysport 和 Botox 的 MED 分别为 10 U 和 7.5 U。关于 VC，只有 10 U 的 Dysport 和 7.5 U 的 Botox 与 V 相比，BP 显著降低（分别从 3.7±0.6 降至 1.5±0.1 和 1.4±0.3mm Hg；p<0.01 和 p<0.001）。Dysport（10 U）和 Botox（7.5 U）通过降低振幅（分别从 7.4±1.1 降至 5.8±0.5 和 5.4±0.6mm Hg；p<0.05）；频率（从 2.2±0.4 降至 1.5±0.2 和 1.3±0.3 次/分钟，分别；p<0.01）；和增加产生 NVC 的体积阈值（分别从 29.8±3.7 升至 47.6±6.9 和 47.7±6.3%；p<0.05 和 p<0.001），显著抑制 NVC。
这是第一项 Dysport 和 Botox 的临床前剂量范围研究，在标准化条件下显示出对 NDO 的相似抑制作用，尽管 MED 不同。它强调了区分每种制剂以预测结果和使用剂量的重要性。需要进一步的 NDO 患者研究来证实这些实验结果。
